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Breast cancer (BC) is one of the most life-threatening diseases of women's health worldwide. This work was conducted to assess the anti-BC potency of a new Zn(II)-based complex. The Zn(II) complex coordinated to dimethoxy-substituted bipyridine was synthesized and its molecular structure was elucidated as [Zn( 2Meo bpy) 3 ](clo 4 ) 2 ( 2Meo bpy-Zn) by single-crystal X-ray diffraction, 2Meo bpy represents 4,4'-dimethoxy-2,2'-bipyridine. The cytotoxicity results indicated that 2Meo bpy-Zn, unlike cisplatin, acts potently and selectively on the human breast cancer cells (MCF-7) compared to normal murine embryo cells (NIH/3T3) by IC 50 value of 4.6 ± 0.5 µm and selectivity index (SI) of 2.0 over 48 h. 2Meo bpy-Zn and cisplatin showed anti-metastatic activity as evidenced by inhibition of the colony formation and cell migration. The flow cytometric assessment of MCF-7 cells supported that 2Meo bpy-Zn and cisplatin exert their cytotoxic effect through the apoptotic pathway. Moreover, 2Meo bpy-Zn could induce overproduction of intracellular reactive oxygen species (ROS) in MCF-7 cells. The apoptotic mechanism in 2Meo bpy-Zn-treated MCF-7 cells is probably related to the regulation of apoptosis-relevant genes expression, including BAX and BCL2. Moreover, 2Meo bpy-Zn is able to cleave pUC19 plasmid DNA through the hydrolytic reaction pathway. Finally, 2Meo bpy-Zn's affinity towards antiapoptosis-related proteins, as a potential apoptosis inducer, as well as breast cancer-relevant proteins, as a potential anti-BC agent, was evaluated by in silico molecular docking studies. Altogether, the results of this work strongly evidenced that 2Meo bpy-Zn can be the subject of experimental validation and clinical trials to introduce this complex as a promising BC therapeutic agent., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Magnetic nanoparticles (MNPs), particularly iron oxide nanoparticles (IONPs), are a fascinating group of nanoparticles that have been considerably investigated for biomedical applications because of their superparamagnetic properties, biodegradable nature, and biocompatibility. A novel Gram-positive moderately thermophilic bacterial strain, namely Bacillus tequilensis ASFS.1, was isolated and identified. This strain is capable of producing superparamagnetic Fe 3 O 4 nanoparticles and exhibiting magnetotaxis behavior. This strain swimming behavior was investigated under static and dynamic environments, where it behaved very much similar to the magnetotaxis in magnetotactic bacteria. This study is the first report of a bacterium from the Bacillaceae family that has the potential to intracellular biosynthesis of IONPs. MNPs were separated by a magnetic and reproducible method which was designed for the first time for this study. In addition, UV-visible spectrophotometer, Fourier-transform infrared spectroscopy, vibrating sample magnetometer, field emission scanning electron microscopy (FESEM), X-ray diffraction, and thermal gravimetric analysis were utilized to characterize the bio-fabricated magnetite nanoparticles. Analysis of the particle size distribution pattern of the biogenic MNPs by FESEM imaging revealed the size range of 10-100 nm with the size range of 10-40 nm MNPs being the most frequent particles. VSM analysis demonstrated that biogenic MNPs displayed superparamagnetic properties with a high saturation magnetization value of 184 emu/g. After 24 h treatment of 3T3, U87, A549, MCF-7, and HT-29 cell lines with the biogenic MNPs, IC 50 values were measured to be 339, 641, 582, 149, and 184 μg mL -1 , respectively. This study presents the novel strain ASFS.1 capable of magnetotaxis by the aid of its magnetite nanoparticles and paving information on isolation, characterization, and in vitro cytotoxicity of its MNPs. The MNPs showed promising potential for biomedical applications, obviously subject to additional studies., (© 2024 Wiley‐VCH GmbH.)

One of the most challenging tasks in modern medicine is to find novel efficient cancer therapeutic methods with minimal side effects. The recent discovery of several classes of organic molecules known as "molecular jackhammers" is a promising development in this direction. It is known that these molecules can directly target and eliminate cancer cells with no impact on healthy tissues. However, the underlying microscopic picture remains poorly understood. We present a study that utilizes theoretical analysis together with experimental measurements to clarify the microscopic aspects of jackhammers' anticancer activities. Our physical-chemical approach combines statistical analysis with chemoinformatics methods to design and optimize molecular jackhammers. By correlating specific physical-chemical properties of these molecules with their abilities to kill cancer cells, several important structural features are identified and discussed. Although our theoretical analysis enhances understanding of the molecular interactions of jackhammers, it also highlights the need for further research to comprehensively elucidate their mechanisms and to develop a robust physical-chemical framework for the rational design of targeted anticancer drugs.

Hepatocellular carcinoma is the most common type of primary liver cancer. However, multidrug resistance (MDR) is a major obstacle to the effective chemotherapy of cancer cells. This report documents the rational design, synthesis, and biological evaluation of a novel series of triazolotriazines substituted with CH 2 NH-linked pyridine for use as dual c-Met/MDR inhibitors. Compound 12g with IC 50 of 3.06 μM on HepG2 cells showed more potency than crizotinib (IC 50  = 5.15 μM) in the MTT assay. In addition, 12g inhibited c-Met kinase at a low micromolar level (IC 50  = 0.052 μM). 12g significantly inhibited P-gp and MRP1/2 efflux pumps in both cancerous HepG2 and BxPC3 cells starting from the lower concentrations of 3 and 0.3 µM, respectively. 12g did not inhibit MDR1 and MRP1/2 in noncancerous H69 cholangiocytes up to the concentration of 30 and 60 µM, respectively. Current results highlighted that cancerous cells were more susceptible to the effect of 12g than normal cells, in which the inhibition occurred only at the highest concentrations, suggesting a further interest in 12g as a selective anticancer agent. Overall, 12g, as a dual c-Met and P-gp/MRP inhibitor, is a promising lead compound for developing a new generation of anticancer agents., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

A database of 300 compounds was virtually screened and docked against Bcl-2 protein; the stability of the best-formed complex was evaluated through Molecular dynamics, the top ten compounds with the best in-silico complexation affinities were synthesized, and their In-vitro cytotoxic activity was examined. Thiazolidinone (4e) and isoxazoline (4a-d) were evaluated in-silico . For further evaluation and examination, we designed and synthesized from naturally occurring (R)-carvone and characterized it via spectroscopic analysis, as well as tested for their anticancer activities towards human cancer cell lines such as HT-1080 (fibrosarcome cancer), MCF-7 and MDA-MB-231 (breast cancer) and A-549 (lung cancer) by using MTT method with Doxorubicin as standard drug. Among them, compound 4d showed the most promising anticancer activity against HT-1080, A-549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 15.59 ± 3.21 µM; 18.32 ± 2.73 µM; 17.28 ± 0.33 µM and 19.27 ± 2.73 µM respectively.Communicated by Ramaswamy H. Sarma.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse effect of cisplatin. The current study aimed to determine whether PEGylated nanoliposomal cisplatin can limit CIPN in an animal model., Methods: Cisplatin-loaded PEGylated liposome nanoparticles (Cis-PL) were produced as a combination of lecithin, cholesterol, and DSPE-mPEG2000 in a molar ratio of 50:45:5 and were characterized by polydispersity index (PDI), zeta potential, Field emission scanning electron microscopy (FESEM) analysis, as well as encapsulation efficiency (EE). Fifteen male rats were provided and randomly divided into 3 groups including Cis-PL group, cisplatin group, and control group. Behavioural tests (hot-plate test and acetone drop test) were used for evaluating CIPN. Moreover, oxidative stress markers and histopathological analysis were applied. Treatment-related toxicity was assessed by haematological analysis as well as liver and renal function tests., Results: Cis-PL had an average particle size of 125.4, PDI of 0.127, and zeta potential of -40.9 mV. Moreover, the Cis-PL exhibited a high EE as well as low levels of leakage rate at 25 °C. In a hot-plate test, paw withdrawal latency was longer in Cis-PL group in comparison to rats treated with cisplatin. A lower number of withdrawal responses was detected during acetone drop test in Cis-PL group than in cisplatin-treated rats. Assessment of oxidative stress markers showed that Cis-PL could improve oxidative stress. Additionally, histopathological assessment demonstrated that the number of satellite cells was significantly reduced in the dorsal root ganglion (DRG) of Cis-PL-treated rats compared with those treated with cisplatin. The cisplatin group had elevated white blood cells counts, reduced platelet counts, and higher levels of bilirubin, ALT (alanine aminotransferase, and AST (aspartate aminotransferase), and creatinine compared with the control group, which was ameliorated in Cis-PL group., Conclusions: Data from the current study support the previous hypothesis that Cisplatin-loaded PEGylated liposome could be a promising solution for CIPN in the future by modulating oxidative stress and preventing glial cell activation in DRG, suggesting further clinical studies to investigate the efficacy of this agent and its potential application in clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cancer continues to be leading cause of morbidity and mortality despite decades of research and advancement in chemotherapy. Most tumors can be reduced via standard oncology treatments, such as chemotherapy, radiotherapy, and surgical resection, and they frequently recur. Significant progress has been made since targeted cancer therapy inception in creation of medications that exhibit improved tumor-selective action. Particularly in preclinical and clinical investigations, fusion proteins have shown strong activity and improved treatment outcomes for a number of human cancers. Synergistically combining many proteins into one complex allows the creation of synthetic fusion proteins with enhanced characteristics or new capabilities. Signal transduction pathways are important for onset, development, and spread of cancer. As result, signaling molecules are desirable targets for cancer therapies, and significant effort has been made into developing fusion proteins that would act as inhibitors of these pathways. A wide range of biotechnological and medicinal applications are made possible by fusion of protein domains that improves bioactivities or creates new functional combinations. Such proteins may function as immune effectors cell recruiters to tumors or as decoy receptors for various ligands. In this review article, we have outlined the standard methods for creating fusion proteins and covered the applications of fusion proteins in treatment of cancer. This article also highlights the role of fusion proteins in targeting the signaling pathways involved in cancer for effective treatment., (© 2023 International Union of Biochemistry and Molecular Biology, Inc.)

Lysine Specific Demethylase 1 (LSD1) has been identified as a chromatin-modifying enzyme implicated in various cancer pathogeneses, highlighting the potential for novel epigenetic cancer treatments through the development of effective inhibitors. We employed 3D-QSAR pharmacophore modeling, molecular docking, and molecular dynamics simulations to identify a promising drug candidate for LSD1 inhibition. RMSD, RMSF, H-bond, and DSSP analysis demonstrated that ZINC02599970 (Arformoterol) and ZINC13453966 exhibited the highest LSD1 inhibitory potential. Experimental validation using MCF-7 and MDA-MB-231 cell lines revealed that Arformoterol displayed potent antiproliferative activity with IC 50 values of 12.30 ± 1.48 μM and 19.69 ± 1.15 μM respectively. In contrast, the IC 50 values obtained for the control (tranylcypromine) in exposure to MCF-7 and MDA-MB-231 cells were 104.6 ± 1.69 μM and 77 ± 0.67 μM, respectively. Arformoterol demonstrated greater LSD1 inhibitory potency in MCF-7 cells compared to MDA-MB-231 cells. Also, the expression of genes involved in chromatin rearrangement (LSD1), angiogenesis (VEGF1), cell migration (RORα), signal transduction (S100A8), apoptosis, and cell cycle (p53) were investigated. Arformoterol enhanced apoptosis and induced cell cycle arrest at the G2/M phase, both in MCF-7 and MDA-MB-231 cancer cells. Based on our findings, we propose that Arformoterol represents a promising candidate for breast cancer treatment, owing to its potent LSD1 inhibitory activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Monoamine oxidases (MAOs) and vascular endothelial growth factor receptor-2 (VEGFR-2) are promoters of colorectal cancer (CRC) and central signaling nodes in epithelial-mesenchymal transition (EMT) induced by activating hypoxia-inducible factors (HIFs). Herein, a novel series of rationally designed triazole-tethered quinoxalines were synthesized and evaluated against HCT-116 CRC cells. The tailored scaffolds combine the pharmacophoric themes of both VEGFR-2 inhibitors and MAO inhibitors. All the synthesized derivatives were screened utilizing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for their possible cytotoxic effects on normal human colonocytes, then evaluated for their anticancer activities against HCT-116 cells overexpressing MAOs. The hit derivatives 11 and 14 exhibited IC 50  = 18.04 and 7.850 µM, respectively, against HCT-116cells within their EC 100 doses on normal human colonocytes. Wound healing assay revealed their efficient CRC antimetastatic activities recording HCT-116 cell migration inhibition exceeding 75 %. In vitro enzymatic assays demonstrated that both 11 and 14 efficiently inhibited VEGFR-2 (IC 50  = 88.79 and 9.910 nM), MAO-A (IC 50  = 0.763 and 629.1 nM) and MAO-B (IC 50  = 0.488 and 209.6 nM) with observed MAO-B over MAO-A selectivity (SI = 1.546 and 3.001), respectively. Enzyme kinetics studies were performed for both compounds to identify their mode of MAO-B inhibition. Furthermore, qRT-PCR analysis showed that the hits efficiently downregulated HIF-1α in HCT-116cells by 3.420 and 16.96 folds relative to untreated cells. Docking studies simulated their possible binding modes within the active sites of VEGFR-2 and MAO-B to highlight their essential structural determinants of activities. Finally, they recorded in silico drug-like absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles as well as ligand efficiency metrics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: This study explores the cytotoxic and apoptotic effects of novel thiazolidinone-1,2,3-triazole hybrids on HT-1080, A-549, and MDA-MB-231 cancer cell lines. Methods & results: The synthesized compounds underwent comprehensive characterization (NMR and HRMS) to confirm their structures and purity. Subsequent anticancer activity screening across diverse cancer cell lines revealed promising antitumor potential notably, compounds 6f and 6g . Mechanistic investigations unveiled that compound 6f triggers apoptosis through the caspase-3/7 pathway. In terms of in silico studies, the compound 6f was identified as a potent inhibitor of caspase-3 and caspase-7. Conclusion: The present study underscores the therapeutic potential of thiazolidinone-1,2,3-triazole hybrids against certain cancer cells. These findings highlight a promising avenue for the development of cancer treatment strategies utilizing these (R)-Carvone-based derivatives.

Aim: A series of semicarbazone and thiosemicarbazone-tailed hybrids comprising pyrazole and acetylisoxazoline were prepared from (R)-carvone and characterized by technique spectroscopies Nuclear Magnetic Resonance (NMR), IR and High-Resolution Mass Spectrometry. Density Functional Theory (DFT) determined the structural parameters. Their cytotoxic activity was evaluated in vitro against four human cancer cell lines. Methods & results: All the studied semi and thiosemicarbazone demonstrate a promising potential as anticancer agents. The mechanism of action of these compounds involves apoptosis in HT-1080 cells, supported by an increase in the level of caspase-3/7 activity, which also arrests the cell cycle in the G0/G1 phase. Molecular docking studies were performed to establish the potential of the most active compounds 4a and 5a . ADMET analysis showed appropriate pharmacokinetic properties, allowing structure prediction for anticancer activity.

Aims and Background: Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc. )., Objective: Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects., Methods: In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay., Results: The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells., Conclusion: It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: A series of (R)-Carvone-based 1,2,3-triazole-thiazolidinone 17a-h hybrids were synthesized and characterized by spectroscopic techniques NMR and HRMS. The chemical reactivity and the stability parameters were observed via DFT. Method/results: The objective was to evaluate the anticancer activity of the synthesized compounds against cancer cell lines. The mechanism of action by which the 17b and 17g exert their effect suggested that they may induce apoptosis through activation of caspase-3/7. This effect was observed against the most important NIMA-related kinases via Docking investigation. The designed compounds were identified as the best inhibitors of the NEK family via the inactivation of the caspase-3. The Docking results were supported by Dynamics where the binding energies justified the medicinal importance of the synthesized derivatives.

Pharmaceutical substance sitagliptin has long been used to treat diabetes. However, subsequent researches have shown that sitagliptin has additional therapeutic effects. Anti-inflammatory effects are observed. Combining sitagliptin with biodegradable polymers like nanoparticles for chemotherapy may be effective. This method enhances therapeutic agent pharmacokinetics. This study tests sitagliptin (SIT) chitosan base nanoparticles against MCF-7 cancer cell lines for anti-cancer effects. Sitagliptin chitosan-based nanoparticles are tested for their ability to suppress MCF-7 cancer cell proliferation. Ionic gelation, a typical nanoparticle manufacturing method, was used. A detailed examination of the nanoparticles followed, using particle-size measurement, FTIR and SEM. Entrapment efficiency, drug-loading, and in-vitro drug release were assessed. Loaded with chitosan and sitagliptin, the nanoparticles averaged 500nm and 534nm in diameter. Sitagliptin has little effect on particle size. Chitosan-based Sitagliptin nanoparticles grew slightly, suggesting Sitagliptin is present. SIT-SC-NPs had 32% encapsulation efficiency and 30% drug content due to their high polymer-to-drug ratio. SEM analysis showed that both drug-free and sitagliptin-loaded nanoparticles are spherical, as shown by the different bands in the photos. The SIT-CS-NPs had a 120-hour release efficiency of up to 80%. This suggests that these nanoparticles could cure hepatocellular carcinoma, specifically MCF-7 cell lines.

Background: This study aimed to develop novel isoxazoline-1,3,4-thiadiazole hybrids from (S)-verbenone for potential anticancer treatment, particularly focusing on cytotoxic and apoptotic effects in hormone-sensitive MCF-7 and triple-negative MDA-MB-231 breast cancer cells. Methods & results: (S)-verbenone was used to synthesize hybrids through 1,3-dipolar cycloaddition, followed by thorough characterization. The compounds were screened across cancer cell lines, showing significant anticancer effects. Compound 8b notably induced apoptosis via the caspase-3/7 pathway and cell cycle arrest, displaying noteworthy cytotoxicity against MCF-7 and MDA-MB-231 cells. Conclusion: These findings underscore the potential of (S)-verbenone isoxazoline-1,3,4-thiadiazole derivatives for breast cancer therapy due to their remarkable apoptotic activity. This study highlights a promising avenue for advancing breast cancer treatment using these derivatives, founded on (S)-verbenone, showcasing their distinct potential for inducing apoptosis.

Chemotherapy-induced peripheral neuropathy (CIPN) is an important adverse effect of treatment with oxaliplatin (OXA). We have developed PEGylated nanoliposomal oxaliplatin (OXA-LIP) and tested its activity in an animal model of CIPN. OXA-LIPs were prepared using a combination of egg yolk lecithin, cholesterol, and DSPE-mPEG2000 (at ratios 400, 80, and 27 mg). These liposomes were characterized using several different methods (e.g., polydispersity index (PDI), and zeta potential, FESEM). The in vivo study was performed in 15 male rats comprising three groups: a negative control (normal saline) OXA, and OXA-LIP. These were injected intraperitoneally at a concentration of 4 mg/kg on two consecutive days every week, for 4 weeks. After that, CIPN was assessed using the hotplate and acetonedropmethods. Oxidative stress biomarkers such as SOD, catalase, MDA, and TTG were measured in the serum samples. The functional disturbances of the liver and kidney were assessed by measuring the serum levels of ALT, AST, creatinine, urea, and bilirubin. Furthermore, hematological parameters were determined in the three groups. The OXA-LIP had an average particle size, PDI, and zeta potential of 111.2 ± 1.35 nm, 0.15 ± 0.045, and -52.4 ± 17 mV, respectively. The encapsulation efficiency of OXA-LIP was 52% with low leakage rates at 25 °C.Thermal hyperalgesia changes showed OXA has significant effects in the induction of neuropathy on days 7, 14, and 21 compared to the control group. OXA had a significantly greater sensitivity than the OXA-LIP and control groups in the thermal allodynia test (P < 0.001). OXA-LIP administration did not show significant effects on the changes of oxidative stress, biochemical factors, and cell count. Our findings provide a proof of concept on the potential application of oxaliplatin encapsulated with PEGylated nanoliposome to ameliorate the severity of neuropathy, supporting further studies in clinical phases to explore the value of this agent for Chemotherapy-induced peripheral neuropathy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Exosomes have recently been considered ideal biotherapeutic nanocarriers that broaden the frontiers of current drug delivery systems to overcome the shortcomings associated with cytokine-based immunotherapy. Using this approach, the current study aimed to assess anti-proliferative activity of purified IL-29 and exosomes encapsulated IL-29. The IL-29+pET-28a construct was transformed into Rosetta 2(DE3) cells which was used for the large-scale production of IL-29. Exosomes isolated from H1HeLa, and SF-767 cells using Total Exosome Isolation reagent were loaded with IL-29 via sonication. Isolation of exosomes was validated using their core protein signature by western blotting and specific miRNA profiles by RT-PCR. The drug loading efficiency of exosomes derived from H1HeLa cells was higher than that of SF-767-derived exosomes. The drug release kinetics of IL-29 encapsulated exosomes exhibited stable release of the recombinant drug. Around 50% of all cancer cell lines survived when IL-29 was administered at a concentration of 20 µg/mL. A survival rate of less than 10% was observed when cells were treated with 20 µg/mL IL-29 loaded exosomes. It was concluded that IL-29 loaded exosomes had a more significant cytotoxic effect against cancer cells, which might be attributed to sustained drug release, improved half-life, superior targeting efficacy, capacity to harness endogenous intracellular trafficking pathways, and heightened biocompatibility of exosomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

3-Amino-2-arylcarboxamido-thieno[2-3- b ]pyridines have been previously described as having potent anti-proliferative activity against MDA-MB-231 and HCT116 cancer cell lines. The mechanism by which these molecules prevent cancer cell growth is proposed to be through interfering with phospholipid metabolism via inhibition of PI-PLC, along with other cellular processes. Previously, 5-cinnamyl derivatives of these thieno[2-3- b ]pyridines have been shown to have enhanced anti-proliferative activity compared to compounds lacking this moiety, indicating a tethered aromatic ring is important for this western region of the pharmacophore. Herein, we report the synthesis and biological evaluation of a library of 40 novel thieno[2-3- b ]pyridine analogues containing shorter benzoyl or secondary benzyl alcohol tethers at the 5-position, in addition to various substituents on the two phenyl rings present on the molecule. Compounds bearing alcohol functionality had improved efficacy compared to their benzoyl counterparts, in addition to a 2-methyl-3-halogen substitution on the 2-arylcarboxamide ring being important for maximising anti-proliferative activity. The most potent molecules 7h and 7i demonstrated IC 50 concentrations of 25-50 nM against HCT116 and MDA-MB-231 cells, a similar level of activity as previous thienopyridine compounds bearing cinnamyl moieties, suggesting that these novel derivatives with shorter tethers were able to maintain potent anti-proliferative activity, while allowing for a more concise synthesis.

Cancer is a leading cause of death worldwide, but advances in treatment, early detection, and prevention have helped to reduce its impact. To translate cancer research findings into clinical interventions for patients, appropriate animal experimental models, particularly in oral cancer therapy, can be helpful. In vitro experiments using animal or human cells can provide insight into cancer's biochemical pathways. This review discusses the various animal models used in recent years for research and clinical intervention in oral cancer, along with their advantages and disadvantages. We highlight the advantages and limitations of the used animal models in oral cancer research and therapy by searching the terms of animal models, oral cancer, oral cancer therapy, oral cancer research, and animals to find all relevant publications during 2010-2023. Mouse models, widely used in cancer research, can help us understand protein and gene functions in vivo and molecular pathways more deeply. To induce cancer in rodents, xenografts are often used, but companion animals with spontaneous tumours are underutilized for rapid advancement in human and veterinary cancer treatments. Like humans with cancer, companion animals exhibit biological behaviour, treatment responses, and cytotoxic agent responses similar to humans. In companion animal models, disease progression is more rapid, and the animals have a shorter lifespan. Animal models allow researchers to study how immune cells interact with cancer cells and how they can be targeted specifically. Additionally, animal models have been extensively used in research on oral cancers, so researchers can use existing knowledge and tools to better understand oral cancers using animal models., (© 2023 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Immunogenic Cell Death (ICD) is a type of cell death that kills tumor cells by stimulating the adaptive immune response against other tumor cells. ICD depends on the endoplasmic reticulum (ER) stress and the secretion of Damage-Associated Molecular Patterns (DAMP) by the dying tumor cell. DAMPs recruit innate immune cells such as Dendritic Cells (DC), triggering a cancer-specific immune response such as cytotoxic T lymphocytes (CTLs) to eliminate remaining cancer cells. ICD is accompanied by several hallmarks in dying cells, such as surface translocation of ER chaperones, calreticulin (CALR), and extracellular secretion of DAMPs such as high mobility group protein B1 (HMGB1) and adenosine triphosphate (ATP). Therapeutic peptides can kill bacteria and tumor cells thus affecting the immune system. They have high specificity and affinity for their targets, small size, appropriate cell membrane penetration, short half-life, and simple production processes. Peptides are interesting agents for immunomodulation since they may overcome the limitations of other therapeutics. Thus, the development of peptides affecting the TME and active antitumoral immunity has been actively pursued. On the other hand, several peptides have been recently identified to trigger ICD and anti-cancer responses. In the present review, we review previous studies on peptide-induced ICD, their mechanism, their targets, and markers. They include anti-microbial peptides (AMPs), cationic or mitochondrial targeting, checkpoint inhibitors, antiapoptotic inhibitors, and "don't eat me" inhibitor peptides. Also, peptides will be investigated potentially inducing ICD that is divided into ER stressors, ATPase inhibitors, and anti-microbial peptides., (Copyright © 2023. Published by Elsevier Masson SAS.)

According to the favorable antitumor properties of selenium, this study aimed to design a novel form of selenium nanoparticles (Se NPs) functionalized with chitosan (Cs) and sialic acid to assess their antitumor effects on the human glioblastoma cell lines (T98 and A172). Se NPs were synthesized in the presence of chitosan and ascorbic acid (Vc) and the synthesis conditions were optimized using response surface methodology. Se NPs@Cs were obtained with a monoclinic structure with an average diameter of 23 nm under the optimum conditions (reaction time = 30 min, chitosan concentration = 1 % w/v, Vc/Se molar ratio = 5). To modify Se NP@Cs for glioblastoma treatment, sialic acid was used to cover the surface of the NPs. Sialic acid was successfully attached to the surface of Se NPs@Cs, and Se NPs@Cs-sialic acid were formed in the size range of 15-28 nm. Se NPs@Cs-sialic acid were stable for approximately 60 days at 4 ℃. The as-synthesized NPs exerted inhibitory effects on T98 greater than 3 T3 > A172 cells in a dose- and time-dependent manner. Additionally, sialic acid ameliorated the blood biocompatibility of Se NPs@Cs. Taken together, sialic acid improved both the stability and biological activity of Se NPs@Cs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Gastric adenocarcinoma (GA) is a serious malignancy with growing incidence and mortality rate worldwide. The objective of the present study was to determine whether 7-geranyloxycoumarin, a natural monoterpene coumarin, could induce anticancer effects, in single use and/or in combination with anticancer drugs and ionizing radiation, on GA cells., Materials and Methods: 7-geranyloxycoumarin was synthesized by a reaction between 7-hydroxycoumarin and transgeranyl bromide. MKN45 cells were treated with 7-geranyloxycoumarin, and the viability of cells was determined by resazurin. Apoptosis was then evaluated by flow cytometric analysis using annexin V and propidium iodide, and the expression of P53 and BCL2 was analyzed by quantitative polymerase chain reaction (qPCR). Combinatorial effects of 7-geranyloxycoumarin with 5-fluorouracil (5-FU), cisplatin (CDDP), and X radiation were also evaluated., Results: Assessment of cell viability indicated that 7-geranyloxycoumarin induced its toxic effects in a time- and dose-dependent manner. This was confirmed by the detection of apoptotic cells, and qPCR results revealed a significant downregulation in BCL2 expression. Although combinatorial use of 7-geranyloxycoumarin + 5-FU or + CDDP did not improve cytotoxicity of anticancer drugs, significant increase in the effectiveness of applied radiations was detected upon pretreatment with 7-geranyloxycoumarin., Conclusion: Our findings provide valuable insights into single and combinatorial effects of 7-geranyloxycoumarin on the GA cells., Competing Interests: None

In this research paper, we report the cytotoxic and apoptotic effects of 1,2,3-triazole derivatives in a unique 7a-g or hybrid form with isoxazoline 8a-g using the eugenol as a precursor in HT-1080 fibrosarcoma, MCF-7, and MDA-MB-231 breast carcinoma, and A-549 lung carcinoma. Data obtained on the cytotoxic effects have shown that hybrid compounds 8a-e induced a significant anticancer activity and are more important than the ones of 1,2,3-triazole derivatives 7a-g with IC 50 ranging from 18 to 43 μM for the hybrids 8a-e and from 15 to 29 μM for mono-adducts 7a-g in all cell lines. Concerning the apoptotic study, compounds 7b and 8a can induce apoptosis in HT-1080 and A-549 cells as revealed by Annexin-V labeling and caspase-3/7 activity, also, the apoptotic effect was accompanied by cell cycle arrest at G2/M phase in the case of compounds 7b and 8a . Both compounds were evaluated in-silico through molecular docking and molecular dynamics and compound 8a is very active against Bcl-2 protein triggering apoptosis phenomenon by intrinsic pathway, therefore compound 8a is a potential candidate to inhibit the anti-apoptotic protein (Bcl-2).Communicated by Ramaswamy H. Sarma.

5-Fluorouracil (5-FU) is a cytotoxic drug with a low half-life. These features can cause some problems such as burst drug release and numerous side effects. In the present study, a pH-sensitive nanocomposite of polyvinylpyrrolidone (PVP)/carboxymethyl cellulose (CMC)/γ-alumina developed by using water in oil in water (W/O/W) double emulsion method. The fabricated emulsion has been employed as the 5-FU carrier to investigate its effects on drug half-life, side effects, drug loading efficiency (DLE), and drug entrapment efficiency (DEE). Analyzing the FTIR and XRD indicated the successful loading of 5-FU into the nanocarrier and affirmed the synthesized nanocomposite's chemical bonding and crystalline features. Furthermore, by using DLS and Zeta potential assessment, size and undersize distribution, as well as the stability of the drug-loaded nanocomposite were determined, which demonstrated the monodisperse and stable nanoparticles. Moreover, the nanocomposites with spherical shapes and homogeneous surfaces were shown in FE-SEM, which indicated good compatibility for the constituents of the nanocomposites. Moreover, by employing BET analysis the porosity has been investigated. Drug release pattern was studied, which indicated a controlled drug release behavior with above 96 h drug retention. Besides, the loading and entrapment efficiencies were obtained 44 % and 86 %, respectively. Furthermore, the curve fitting technique has been employed and the predominant release mechanism has been determined to evaluate the best-fitted kinetic models. MTT assay and flow cytometry assessment has been carried out to investigate the cytotoxic effects of the fabricated drug-loaded nanocomposite on MCF-7 and normal cells. The results showed enhanced cytotoxicity and late apoptosis for the PVP/CMC/γ-alumina/5-FU. Based on the MTT assay outcomes on normal cell lines (L929), which indicated above 90 % cell viability, the biocompatibility and biosafety of the synthesized nanocarrier have been confirmed. Moreover, due to the porosity of the PVP/CMC/γ-alumina, this nanocarrier can exploit from high specific surface area and be more sensitive to environmental conditions such as pH. These outcomes propose that the novel pH-sensitive PVP/CMC/γ-alumina nanocomposite can be a potential candidate for drug delivery applications, especially for cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

New strategies for constructing versatile nanocarriers are needed for cancer therapy to overcome the multiple challenges of targeted delivery. This work explores the advantages of polyurethane with main-chain quaternary ammonium salt moieties (ionene) as a novel carrier for targeted drug delivery. We have developed a novel cationic soybean oil-based polyurethane ionene nanocarrier (CPUI) that can act as an effective anticancer agent and efficiently deliver the anticancer drug 5-fluorouracil (5FU). We also report a potential anticancer drug delivery system targeting the folate receptor. In vitro experiments with blank CPUI carriers on the 4T1 (mouse breast cancer cell line) and the NIH-3T3 (mouse fibroblast cell line) revealed high cytotoxicity for the cancer cells but only low cytotoxicity for the normal fibroblast cells. The CPUI nanoparticles were readily loaded with 5FU (5FU-CPUI) in water using electrostatic interactions between the cationic quaternary ammonium groups of ionene and the anionic 5FU. The in vivo study in mice with tumors showed that the blank CPUI carriers significantly inhibited tumor growth, even more than the free drug (5FU). The inhibitory effect on tumor growth was slightly enhanced when the carriers were loaded with 5FU. The prepared nanoparticles had a high loading capacity of 41.8 %. Further enhancement of the inhibitory effect was observed when folic acid (FA) was added as a targeting moiety to the system via ion exchange with the bromine counterion of the quaternary ammonium moieties. The results suggest that the efficacy of FA-CPUI-5FU nanoparticles as vehicles for drug delivery can be enhanced via folate receptor (FR) mediated endocytosis in 4T1 cells and these novel nanocarriers may provide a potential platform for effective targeted drug delivery to tumor tissue and breast cancer therapy in the clinic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cancer is a complicated, adaptable, and heterogeneous disease caused by a wide variety of genetic changes that might impair ability of cells to function normally. The majority of the tumors can only be shrunk using conventional oncology therapies like chemotherapy, radiation, and surgical resection, and the tumor often recurs. The inability of conventional cancer therapies to completely destroy the Cancer Stem Cells (CSCs) that otherwise lead to therapy resistance is thus addressed by therapeutic approaches that concentrate on targeting CSCs and their micro-environmental niche. In this review, we summarize approaches that are used for the development of fusion proteins and their therapeutic applications for treating cancer. The main purpose of making advancements towards the fusion technology instead of using conventional treatment methods is to achieve a prolonged half-life of the therapeutic drugs. The fusion of drugs to the immune response enhancing cytokines or the fusion of antibody and cytokines not only increases half-life but also increase the stability of the anti-tumor drug. Several molecules including different fragments of antibodies, cytokines, Human Serum Albumin, transferrin, XTEN polymers, Elastin-like polypeptides (ELPs) can be employed as a fusion partner and the resulting fusion proteins are reported to show enhanced anti-tumor response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

This study aimed to analyze the cytotoxic and apoptotic effects of isoxazoline derivatives with monoterpene scaffold 9a-e in HT-1080 fibrosarcoma, MCF-7, and MDA-MB-231 breast carcinoma, and A-549 lung carcinoma. The cytotoxic effects data revealed that compounds 9a-e generally induced significant cell growth inhibition in all cell lines, with IC 50 ranging from 10 to 30 µM. However, for compounds 9c and 9e , the IC 50 reached a value of 100 µM in HT-1080 cells. Compounds 9a , 9b, and 9d could induce apoptosis in HT-1080 cells as demonstrated by Annexin-V labeling and Caspase-3/7 activity. The apoptotic effect was accompanied by cell cycle arrest in the S phase. Molecular docking and molecular dynamics confirmed the empirical assay results and confirmed the stability of the complex with the inhibition of the anti-apoptotic protein, leading to cancer cell death. Overall, these data suggest that the proposed isoxazoline derivatives may be potential candidates for further investigation to evaluate their efficacy and optimal use in cancer treatment.Communicated by Ramaswamy H. Sarma.

Although quercetin (QC) has valuable advantages, its low water solubility and poor permeability have limited its utilization as an anticancer drug. In this study, hydrogel nanocomposite of chitosan (CS), halloysite (HNT), and graphitic‑carbon nitride (g-C3N4) was prepared and loaded by QC using a water in oil in water emulsification process to attain QC sustained-release. Using g-C3N4 in the HNT/CS hydrogel solution enhanced the entrapment effectiveness (EE %) by up to 86 %. The interactions between QC and nanoparticles caused the nanocomposite pH-responsive behavior that assists in minimizing the side effect of the anticancer agent by controlling the burst release of QC at neutral conditions. According to DLS analysis, the size of the QC-loaded nanovehicle was 454.65 nm, showing that nanoparticles are highly monodispersed, which also was approved by FE-SEM. Additionally, Zeta potential value for the fabricated drug-loaded nanocarrier is +55.23 mV displaying that nanoparticles have good stability. The hydrogel nanocomposite structure's completeness was shown by FTIR pattern, and quercetin was included into the designed delivery system based on XRD data. Besides, the drug release profile indicated that a targeted sustained-release and pH-sensitive release of anticancer drug with the 96-hour extended-release were noticed. In order to comprehend the process of QC release at pH 5.4 and 7.4, four kinetic models were employed to find the best-suited model according to the acquired release data. Finally, the MTT experiment revealed considerable cytotoxicity against breast cancer cells, MCF-7 cell line was experimented in vitro, for the CS/HNT/g-C3N4 targeted delivery system in comparison to QC as a free drug. According to the above description, the CS/HNT/g-C3N4 delivery platform is a unique pH-sensitive drug delivery system for anticancer purposes that improves loading as well as sustained-release of quercetin., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

The development of novel therapeutics promoting selective tumor elimination is the mainstay of clinical oncology. Emerging insights into tumor targeting reveal caspases activation, especially caspase-3, as a personalized anticancer strategy. Our on-going cancer research has exploited Passerini α-acyloxy carboxamides as caspase-3/7-dependent apoptotic inducers. Herein, we adopted scaffold hopping design to introduce new series of isoindole-based Passerini adducts as caspase-3/7 activators inspired by natural alkaloids from Lion's Mane mushroom promoting caspase-3-mediated apoptosis. Additional pharmacophoric motifs of lead caspase activators were merged into the tailored Passerini skeleton. The rationally designed adducts were synthesized utilizing one-pot reaction of the novel 4-(2'-phthalimido)phenylisonitrile 5, cyclohexanone and miscellaneous carboxylic acids under Passerini conditions. All derivatives were screened for their antiproliferative activities against lung A549, colorectal Caco-2 and breast MDA-MB 231 cancer cells compared to normal fibroblasts utilizing MTT assay. Most of the evaluated derivatives were superior to 5-fluorouracil. The 2-(1H-indol-3-yl)acetate derivative (8a) recorded the highest anticancer potency (IC 50  = 0.04-0.11 μM) and selectivity (SI = 42.59-125.53), followed by the 3-(4-(trifluoromethyl)phenyl)acrylate (8m), the 2-(phenylsulfonyl)glycinate (8q), and the 2-(2-(3-phenyl-1,2,4-oxadiazol-5-yl)phenoxy)acetate (8c) derivatives, respectively. The four hits induced cancer cells apoptosis (up to 57.99%) via caspase-3/7 activation (up to 5.47 folds). Apoptosis-inducing factor1 (AIF1) quantification assay excluded their caspase-independent apoptosis induction potential via AIF1 signaling pathway. Docking simulations clarified the possible binding modes of the hit compounds with XIAP BIR2 domain; the specific receptor of caspase-3/7 activators, and aided identifying their structural determinants of activity. Finally, their practical LogP, efficiency metrics, in silico ADMET profiling were drug-like., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Multifunctional nanoplatforms based on novel bimetallic nanoparticles have emerged as effective radiosensitizers owing to their potential capability in cancer cells radiosensitization. Implementation of chemotherapy along with radiotherapy, known as synchronous chemoradiotherapy, can augment the treatment efficacy. Herein, a tumor targeted nanoradiosensitizer with synchronous chemoradiotion properties, termed as CuFe 2 O 4 @BSA-FA-CUR, loaded with curcumin (CUR) and modified by bovine serum albumin (BSA) and folic acid (FA) was developed to enhance tumor accumulation and promote the anti-cancer activity while attenuating adverse effects. Both copper (Cu) and iron (Fe) were utilized in the construction of these submicron scale entities, therefore strong radiosensitization effect is anticipated by implementation of these two metals. The structure-function relationships between constituents of nanomaterials and their function led to the development of nanoscale materials with great radiosensitizing capacity and biosafety. BSA was used to anchor Fe and Cu ions but also to improve colloidal stability, blood circulation time, biocompatibility, and further functionalization. Moreover, to specifically target tumor sites and enhance cellular uptake, FA was conjugated onto the surface of hybrid bimetallic nanoparticles. Finally, CUR as a natural chemotherapeutic agent was encapsulated into the developed bimetallic nanoparticles. With incorporation of all abovementioned stages into one multifunctional nanoplatform, CuFe 2 O 4 @BSA-FA-CUR is produced for synergistic chemoradiotherapy with positive outcomes. In vitro investigation revealed that these nanoplatforms bear excellent biosafety, great tumor cell killing ability and radiosensitizing capacity. In addition, high cancer-suppression efficiency was observed through in vivo studies. It is worth mentioning that co-use of CuFe 2 O 4 @BSA-FA-CUR nanoplatforms and X-ray radiation led to complete tumor ablation in almost all of the treated mice. No mortality or radiation-induced normal tissue toxicity were observed following administration of CuFe 2 O 4 @BSA-FA-CUR nanoparticles which highlights the biosafety of these submicron scale entities. These results offer powerful evidence for the potential capability of CuFe 2 O 4 @BSA-FA-CUR in radiosensitization of malignant tumors and opens up a new avenue of research in this area., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Anthracyclines can improve survival in many types of malignancies, but dose-dependent and irreversible results following the use of anthracyclines have been associated with cardiomyopathy. This meta-analysis aimed to compare the effects of prophylactic agents for preventing cardiotoxicity induced following anticancer agents., Methods: In this meta-analysis, Scopus, Web of Science, and PubMed were surfed for articles published by December 30 th , 2020. The keywords were angiotensin-converting enzyme inhibitor (ACEI), enalapril, captopril, angiotensin receptor blocker, beta blocker, metoprolol, bisoprolol, isoprolol, statin, valsartan, losartan, eplerenone, idarubicin, nebivolol, dihydromyricetin, ampelopsin, spironolactone, dexrazoxane, antioxidants, cardiotoxicity, n-acetyl-tryptamine, cancer, neoplasms, chemotherapy, anthracyclines, doxorubicin, daunorubicin, epirubicin, idarubicin, ejection fraction or a combination of them in the titles or abstracts., Results: A total of 17 articles out of 728 studies examining 2,674 patients were included in this systematic review and meta-analysis. Ejection fraction (EF) values in the baseline, 6-month, and 12-month follow-up in the intervention group turned out to be 62.52 ± 2.48, 59.63 ± 4.85, and 59.42 ± 4.53, whereas in the control group appeared to be 62.81 ± 2.58, 57.69 ± 4.32, and 58.60 ± 4.58, respectively. Through comparison of the two groups, EF was found to increase in the intervention group by 0.40 after 6 months (Standardized mean difference (SMD): 0.40, 95% confidence interval (CI): 0.27, 0.54), thus proving higher than that of the control groups following the cardiac drugs., Conclusion: This meta-analysis showed that prophylactic treatment with cardio-protective drugs, including dexrazoxane, beta blocker, and ACEI drugs in patients undergoing chemotherapy with anthracycline, have a protective effect on LVEF and prevent EF drop., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Prostate cancer is the second most prevalent cancer among men. Despite different treatments, including surgery, chemotherapy, radiation therapy, hormone therapy and immunotherapy for this disease, patients ultimately progress to advanced states. Thus, there is a need for new treatment options targeting cell growth and apoptosis to better control the proliferation and metastasis of these cells. There are many reports indicating overexpression of the 15-lipoxygenase-1 (15-LOX-1) enzyme in prostate tumors. Studies have also shown that inhibition of this enzyme prevents the progression of prostate cancer., Objective: This study was conducted to assess the anti-cancer properties of some coumarin derivatives as possible 15- LOX-1 inhibitors, on PC-3 prostate cancer cells., Methods: In this study, the activity of 15-LOX-1 was evaluated in PC-3 cells by a spectrophotometric assay. In addition, due to high similarity between the 15-LOX-1 and soybean 15-lipoxygenase (SLO) (L1; EC 1, 13, 11, 12) active sites, the soybean SLO was used to investigate inhibitory effects of synthetic coumarin compounds 8- isopentenyloxycoumarin (8-IC), 8-isopentenyloxy-3-carboxycoumarin (8-ICC), 8-geranyloxycoumarin (8-GC), 8- geranyloxy-3-carboxycoumarin (8-GCC), and 8-farnesyloxy-3-carboxycoumarin (8-FCC) on this enzyme. Moreover, the cytotoxic and anticancer effects of the coumarin compounds were examined on PC-3 (Prostate Cancer) and HDF-1 (Human Dermal Fibroblast) cells by alamarBlue assay. Finally, apoptosis-inducing effects of all synthetic compounds were determined by flow cytometry., Results: The IC 50 values obtained by the alamarBlue test revealed that 8-IC, 8-GC and 8-GCC had cytotoxic effects on PC-3 cells. Treating both PC-3 and HDF-1 cells with 8-ICC and 8-FCC did not significantly reduce cell number. Furthermore, the IC 50 values of 8-IC on HDF-1 cells showed cytotoxic effects, while treating these cells with 8-GC and 8- GCC did not show any significant cytotoxicity on these normal human fibroblasts. Assessing the ability of 4-MMPB (as a specific inhibitor of 15-LOX-1), 8-GC, and 8-GCC compounds to inhibit SLO revealed that these compounds exerted strong 15-LOX-1 inhibitory activity, while 8-IC and 8-FCC had a weak inhibitory effect and also 8-ICC showed no inhibitory effect on SLO enzyme. In addition, flow cytometric analysis by FITC (fluorescein isothiocyanate)- annexin V and propidium iodide showed that treatment with IC 50 values of 8-GC and 8-GCC induced apoptosis in 35.2% and 30.8% of PC-3 cells, respectively., Conclusion: Thus, 8-GC and 8-GCC can be introduced as effective anticancer agents with apoptosis-inducing properties. Furthermore, our results suggest that the cytotoxic effects of these compounds might be related to the inhibition of 15-LOX-1 enzyme in PC-3 cells. On the other hand, the cytotoxic effects of 8-IC might be due to the inhibition of other signaling pathways in PC-3 cells. However, further in vivo experiments are required to determine the exact mechanisms involved in the anticancer effects of these coumarin compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Colorectal cancer (CRC) is a highly widespread malignancy and ranks as the second most common cause of cancer-related mortality., Objective: Cancer patients, including those with CRC, who undergo chemotherapy, are often treated with platinum- based anticancer drugs such as oxaliplatin (OXA). Nevertheless, the administration of OXA is associated with a range of gastrointestinal problems, neuropathy, and respiratory tract infections. Hence, it is necessary to devise a potential strategy that can effectively tackle these aforementioned challenges. The use of nanocarriers has shown great potential in cancer treatment due to their ability to minimize side effects, target drugs directly to cancer cells, and improve drug efficacy. Furthermore, numerous studies have been published regarding the therapeutic efficacy of nanoparticles in the management of colorectal cancer., Methods: In this review, we present the most relevant nanostructures used for OXA encapsulation in recent years, such as solid lipid nanoparticles, liposomes, polysaccharides, proteins, silica nanoparticles, metal nanoparticles, and synthetic polymer-carriers. Additionally, the paper provides a summary of the disadvantages and limits associated with nanoparticles., Results: The use of different carriers for the delivery of oxaliplatin increased the efficiency and reduced the side effects of the drug. It has been observed that the majority of research investigations have focused on liposomes and polysaccharides., Conclusion: This potentially auspicious method has the potential to enhance results and enhance the quality of life for cancer patients undergoing chemotherapy. However, additional investigation is required to ascertain the most suitable medium for the transportation of oxaliplatin and to assess its efficacy through clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A new series of thiazolidinone linked 1,2,3-triazole hybrids 5a-h was designed and synthesized using the copper-catalyzed Huisgen azide-alkyne cycloaddition (CuAAC) between thiazolidinone linked alkyne and aromatic azides. The structures of the newly synthesized compounds were established by NMR ( 1 H and 13 C) and HRMS. The targeted thiazolidinone-1,2,3-triazole hybrids were evaluated for their cytotoxic activity against four human cancer cell lines, including fibrosarcoma (HT-1080), lung carcinoma (A-549), and breast carcinoma (MCF-7 and MDA-MB-231) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliun bromide (MTT). The obtained data showed that most of these compounds have moderate anti-proliferative activity with IC 50 values between 10.26 ± 0.71 and 53.93 ± 1.20 μM. The compound 5a exhibited higher activity with an IC 50 value of 10.26 ± 0.71 µM, compared to 5d with an IC 50 value of 11.56 ± 1.98 µM for the HT-1080 and MCF-7 cancer cells line, respectively. Moreover, Annexin-V apoptosis was assessed by flow cytometry for hybrid compounds 5a and 5d against HT-1080 and MCF-7 competitor cell lines, as they increase the level of active caspase 3/7. The experimental results were further confirmed by docking studies followed by molecular dynamic simulations. Both the potent derivatives i.e. 5a and 5d have comparable docking scores and MD simulations results showed that the docked complex of 5a is somewhat more stable than 5d primarily for protein p53. The ADMET profile of both derivatives established their safety zone and drug-like potential.Communicated by Ramaswamy H. Sarma.

Selective elimination of tumors has always been the mainstay of oncology research. The on-going research underlying the cellular apoptotic mechanisms reveal caspases activation, especially the key effector caspase-3, as a personalized tumor-selective therapeutic strategy. Our continued research protocol has exploited new optimized Passerini α-acyloxy carboxamides as efficient apoptotic inducers via caspase-3/7 dependent mechanism with highly selective anticancer profiles. The adopted design rationale relied on excluding structural alerts of previous leads, while merging various pharmacophoric motifs of natural and synthetic caspase activators via optimized one-pot Passerini reaction conditions. The prepared compounds resulting from Passerini reaction were screened for their cytotoxic activities against colorectal Caco-2 and liver HepG-2 cancer cells compared to normal fibroblasts utilizing MTT assay. Notably, all compounds exhibited promising low-range submicromolar IC 50 against the studied cancer cell lines, with outstanding tumor selectivity (SI values up to 266). Hence, they were superior to 5-fluorouracil. Notably, 7a, 7g, and 7j conferred the highest potencies against Caco-2 and HepG-2 cells and were selected for further mechanistic studies. Caspas-3/7 activation assay of the hit compounds and flow cytometric analysis of the treated apoptotic cancer cells demonstrated their significant caspase activation potential (up to 4.2 folds) and apoptotic induction capacities (up to 58.7%). Further assessment of Bcl2 expression was performed being a physiological caspase-3 substrate. Herein, the three studied Passerini adducts were able to downregulate Bcl2 in the treated Caco-2 cells. Importantly, the mechanistic studies results of the three hits echoed their preliminary MTT antiproliferative potencies data highlighting their caspase-3 dependent apoptotic induction. Finally, the in silico predicted physicochemical and pharmacokinetic profiles, as well as ligand efficiency metrics were drug-like., (© 2022. The Author(s).)

To improve the efficacy of trastuzumab, it is essential to understand its mechanism of action. One of the significant issues that makes it difficult to determine the precise mechanism of trastuzumab action is the formation of various HER receptor dimers in HER2-positive breast cancer cells. So far, studies have focused on the role of HER2-HER3 heterodimers, and little is known regarding EGFR-HER2 heterodimers. Here, we study the role of trastuzumab on the cell signaling and cell proliferation mediated by EGFR-HER2 heterodimers in BT474 and SRBR3 cells. EGF stimulates the formation of both EGFR homodimer and EGFR-HER2 heterodimer. Trastuzumab only binds to HER2, not EGFR. Therefore, any effects of trastuzumab on EGF-induced activation of EGFR, HER2, and downstream signaling proteins, as well as cell proliferation, are through its effects on EGFR-HER2 heterodimers. We show that trastuzumab inhibits EGF-induced cell proliferation and cell cycle progression in BT474 and SKBR3 cells. Interestingly trastuzumab strongly inhibits EGF-induced Akt phosphorylation and slightly inhibits EGF-induced Erk activation, in both BT474 and SKBR3 cells. These data suggest the presence of a novel mechanism that allows trastuzumab to inhibit EGR-induced Akt activation and cell proliferation, without blocking EGF-induced EGFR-HER2 heterodimerization and activation. We show that trastuzumab inhibits EGF-induced lipid raft localization of the EGFR-HER2 heterodimer. Disruption of the lipid raft with MβCD blocks HER2-mediated AKT activation in a similar way to trastuzumab. MβCD and trastuzumab synergically inhibit AKT activation. We conclude that trastuzumab inhibits EGF-induced lipid raft localization of EGFR-HER2 heterodimer, which leads to the inhibition of Akt phosphorylation and cell proliferation, without blocking the formation and phosphorylation of the EGFR-HER2 heterodimer.

In this study, MgO-doped CNC-g-PAA hydrogel was synthesized by grafting poly (acrylic acid) (PAA) onto cellulose nanocrystals (CNC) and then doped Magnesium oxide (MgO) using pH 7.0 and 12.0 to obtain an efficient nanocomposite hydrogel for antibacterial and anti-cancer activities. The synthesized nanocomposite hydrogels were evaluated by detailed characterization and confirmed the formation of a well-interconnected porous structure. MgO/CNC-g-PAA (pH = 12.0) exhibited improved bactericidal tendencies towards gram-negative and gram-positive bacteria, which was further investigated by in-silico molecular docking analyses and also examined the reactive oxygen species production by photocatalysis and free radical-scavenging assay. After this, Doxorubicin (DOX), a model anticancer drug, was successfully loaded into nanocomposites (∼79 %) by electrostatic interaction and confirmed pH-triggered based release, which was over 53.7 % in 24 h. Finally, in vitro cytotoxicity-based analysis confirmed the improved antitumor efficacy of nanocomposite hydrogels. These findings revealed that MgO/CNC-g-PAA hydrogels might be prospective carriers for controlled drug delivery., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Recently published randomized controlled trials (RCTs) showed improved overall survival (OS) and progression-free survival (PFS) with the combination of immunotherapy and chemotherapy as compared to chemotherapy alone in advanced non-small cell lung cancer (NSCLC). We aimed to provide a systematic review and meta-analysis of RCTs regarding the efficacy and safety of immunotherapy and chemotherapy combinations for advanced NSCLC., Methods: On December 23 rd , 2021, we searched databases for RCTs that reported PFS and OS as primary outcomes., Results: We included 11 RCTs with 6,386 patients (3,850 in the combination therapy group and 2,536 in the chemotherapy group). Combination therapy was associated with an improvement in PFS (HR: 0.60; 95% CI: 0.54, 0.66; P < 0.00001) andOS (HR: 0.77; 95% CI: 0.68, 0.87; P ≤ 0.0001), compared to chemotherapy. There were no significant differences between both groups in terms of treatment-related adverse events (TRAEs) (RR: 1.07; 95% CI: 0.99, 1.16; P = 0.09)., Conclusion: The combination of immunotherapy and chemotherapy as first-line treatment for advanced NSCLC significantly improved PFS and OS compared to chemotherapy alone without a significant increase in the overall TRAEs.

In the current study, natural (R)-carvone was used as starting material for the efficient synthesis of several 1,2,3-triazole derivatives. The produced products were obtained in good yields and characterized by 1 H and 13 C NMR and HRMS analysis. The newly synthesized monoterpenic 1,2,3-triazole 4 and derivatives were analyzed by viability tests (MTT) for their cytotoxic activity against three human cancer cells. Product 5 showed a medium antitumor activity, for which the IC 50 values against selected cells HT-1080, A-549 and MCF-7 were 29.25 μM, 31.62 μM and 26.02 μM, respectively. The regioselectivity of the condensation reaction and the molecular structure of the title compounds were determined by Density Functional Theory (DFT) using B3LYP calculations at 6-311 + G(d,p) level. The orbitals HOMO and LUMO were studied to determine the electronic properties of the synthesized compounds. In addition, the global reactivity indices were used to explain the regioselectivity for the formation of compound 6 , and the theoretical results agree well with the experimental results. Molecular docking and molecular dynamics confirmed the empirical test results and confirmed the stability of the complex during inhibition of the anti-apoptotic protein for killing cancer cells. Communicated by Ramaswamy H. Sarma.

Low intensity focused ultrasound (LIFU) is a novel approach that could activate drug release and considerably improve the delivery of anticancer drug. LIFU treatment has some features like is able to penetrate deep into the tissue and being non-invasive, as a consequence LIFU displays great capability for controlling the drug release and improving the chemotherapy treatment efficiency. The goal of this study is to research the feasibility of the entropy parameter of RF time series of ultrasound backscattered signals for measuring the changes in temperature induced by a LIFU device. Entropy Imaging is a technique for reconstructing ultrasound images based on the average uncertainty of time-series in a signal. Furthermore, the Shannon Entropy can quantify the uncertainty of a random process and is usually used as a measure for the information content of probability distributions. In this study, we use the Entropy Imaging method for measuring the LIFU-induced temperature changes in the deep region of ex vivo porcine tissue samples. The results obtained show that the changes of entropy parameter of RF time series signal are proportional to temperature changes recorded by a calibrated thermocouple in the temperature range of 37-47°C. In conclusion, in this study we show that Shannon entropy of RF time series signal possesses promising features like succinctly capturing the available information in a system by considering the uncertainty in a given data that can be used, as a new method, to measure temperature changes non-invasively and quantitatively in the deep region of tissue.

Commercial X-ray computed tomography (CT) contrast agents (CAs) are not appropriate for multicolor CT imaging and are limited due to a lack of tumor targeting. In this contribution, to favor the combination of high Z elements like bismuth and iodine for a broad range of X-ray photon energy, BiOI nanoparticles (NPs) are synthesized with hyaluronic acid (HA) coating to target the tumor cells with CD44 overexpression. The crystal structure of BiOI NPs is determined by X-ray powder diffraction, and the size of NPs is determined by a transmission electron microscope at about 14 ± 3 nm. The dynamic diameter of the NPs (DLS) in PBS buffer was measured at about 100 nm. Fourier transform infrared spectroscopy and thermal gravimetric analysis confirm the coating of BiOI NPs with HA. The stability of the NPs was also investigated via UV-vis spectroscopy. The immunocytochemistry process is performed to investigate the targeting ability of synthesized NPs on the human colon cancer cells with CD44 antigen. Finally, the X-ray attenuation of prepared HA-coated BiOI NPs is higher than Iohexol as the commercially available iodinated contrasting agent at the same concentrations, which can be administrated at much lower doses to achieve similar contrast to Iohexol., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In the current study, natural (R)-carvone was utilized as a starting material for the efficient synthesis of two series of isoxazoline derivatives bearing the 1,3,4-thiadiazole moiety. The new compounds were obtained in good yields and were characterized by 1 H and 13 C NMR and HRMS analysis. The newly synthesized monoterpenic isoxazoline 1,3,4-thiadiazole and their thiosemicarbazone intermediate derivatives were evaluated for their anticancer activity in four cancer cell lines (HT-1080, A-549, MCF-7, and MDA-MB-231). Most of the synthesized compounds exhibited moderate to high anticancer effects. Compound 13c showed the highest anticancer activity with IC 50 values ranging from 19.33 ± 1.81 to 34.81 ± 3.03 µM. Further investigation revealed that compounds 12e and 13c could inhibit the cell growth of HT-1080 and MCF-7 cells by inducing apoptosis through caspase-3/7 activation. The apoptotic effect was accompanied by an S phase and G2/M cell cycle arrest for 13c and 12e, respectively. Compounds 12e and 13c were assessed in silico using molecular docking and molecular dynamics. We found that compound 13c is moderately active against the caspase-3 protein, which triggers apoptosis via intrinsic and extrinsic routes, making compound 13c a promising candidate to activate the proapoptotic protein (caspase-3)., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Curcumin application as an anti-cancer drug is faced with several impediments. This study has developed a platform that facilitates the sustained release of curcumin, improves loading efficiency, and anti-cancer activity. Montmorillonite (MMT) nanoparticles were added to chitosan (CS)-agarose (Aga) hydrogel and then loaded with curcumin (Cur) to prepare a curcumin-loaded nanocomposite hydrogel. The loading capacity increased from 63% to 76% by adding MMT nanoparticles to a chitosan-agarose hydrogel. Loading the fabricated nanocomposite in the nanoniosomal emulsion resulted in sustained release of curcumin under acidic conditions. Release kinetics analysis showed diffusion and erosion are the dominant release mechanisms, indicating non-fickian (or anomalous) transport based on the Korsmeyer-Peppas model. FTIR spectra confirmed that all nanocomposite components were present in the fabricated nanocomposite. Besides, XRD results corroborated the amorphous structure of the prepared nanocomposite. Zeta potential results corroborated the stability of the fabricated nanocarrier. Cytotoxicity of the prepared CS-Aga-MMT-Cur on MCF-7 cells was comparable with that of curcumin-treated cells (p < 0.001). Moreover, the percentage of apoptotic cells increased due to the enhanced release profile resulting from the addition of MMT to the hydrogel and the incorporation of the fabricated nanocomposite into the nanoniosomal emulsion. To recapitulate, the current delivery platform improved loading, sustained release, and curcumin anti-cancer effect. Hence, this platform could be a potential candidate to mitigate cancer therapy restrictions with curcumin., (© 2022 American Institute of Chemical Engineers.)

A series of novel 2-iminothiazolidin-4-one analogs have been synthesized from limonaketone, and structurally characterized by HR-MS, 1 H-NMR and 13 C-NMR spectroscopy techniques, and the structure of compound 4 was elucidated by XRD. The newly synthesized products were biologically evaluated in vitro for their cytotoxic activity against human cancer cell lines HT-1080, A549, and MCF-7. Thiazolidinones 9 and 10 were the most active compounds in HT-1080 cell lines (IC 50 =15.85±1.75 and 16.13±1.55 μM, respectively). The apoptosis induction of the derivatives 9 and 10 were studied using annexin V staining, caspase-3/7 activity and cell cycle analysis. Compound 10 showed the highest ability of apoptosis induction and caspase-3/7 activation associated with S-phase growth arrest in HT-1080. Meanwhile, compound 9 has a moderate apoptotic effect and G0/G1-phase arrest in the after-mentioned cell. The molecular docking suggested that compounds 9 and 10 formed stable ligand-caspase-3 complexes. Besides, the presence of phenyl moiety in ligand 10 is responsible for the enhancement of the caspase-3 activation by the apparition of two additional hydrogen bonds with Cys163 and Gln161amino acids., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Immune checkpoint blockade, considered a revolutionary approach in cancer treatment, is only effective in patients with high tumor-infiltrating lymphocytes (TILs). This work aimed to investigate the feasibility of targeted contrast agent (CA) based on dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs-DEX) for TILs detection by magnetic resonance imaging (MRI) studies. To do so, we synthesized an MRI CA by conjugating SPIONs-DEX to an anti-CD3 monoclonal antibody via cyanogen bromide as a cross-linker. In vitro assessments demonstrated the higher labeling efficiency of the developed CA to CD3+ lymphocytes compared to SPIONs-DEX. In vivo MRI of a xenograft model of CD3+ lymphocytes revealed the significant signal loss after the intravenous injection of the bioconjugate by ∼34 % and 21 % in T 2 *-weighted and T 2 -weighted images, respectively. The histopathological evaluation of xenograft tumors confirmed the labeling of lymphocytes by the targeted CA. This approach could open up a new horizon in the non-invasive assessment of TILs to identify patients eligible for immunotherapy., (© 2022 Wiley-VCH GmbH.)

A computational study was carried out to develop quantitative-structure activity relationship (QSAR), pharmacophore, molecular docking and molecular dynamics simulations of a series of N9-substituted harmine derivatives in order to investigate the structural factors involved in the cytotoxic activity and thus design new active derivatives. A valid 3 D-QSAR (R 2 = 0.89, q 2 =0.67, R 2 pred = 0.72) and 2 D-QSAR (R 2 = 0.81, q 2 =0.69, R 2 pred = 0.76) models were obtained correlating the cytotoxic activity with hydrophobic and hydrogen bond acceptor (HBA) features for 3 D-QSAR and SlogP and a&#95;acc descriptors for 2 D-QSAR. Analysis of the selected descriptors for both models highlighted that lipophilicity and hydrogen bonding acceptor atoms remain the crucial properties and those on which cytotoxic activity depends. Also, these findings are in agreement with the characteristics of the generated pharmacophore. Furthermore, molecular docking revealed that the binding energy (-9.74 kcal/mol) and inhibition constant (0.071 µmol) correlate with the activity of the most active compound that forms hydrophobic interactions and two hydrogen bonds with the the dual specificity tyrosine phosphorylation regulated kinase 1 A (DYRK1A). The molecular dynamics simulations revealed that the protein-ligand equilibrium is stable after 100000 fs of trajectories. Based on these results, we designed new N 9 -substituted harmine derivatives with improved properties: predicted cytotoxic activities, estimated binding energies, estimated inhibition constants and interaction modes with amino acid residues of DYRK1A, compared to the best compound in the studied dataset. Additionally, these newly designed inhibitors showed promising results in the preliminary in silico Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) evaluations.Communicated by Ramaswamy H. Sarma.

Aim: A series of 1,3,4-thiadiazole himachalene hybrids were prepared from the treatment of a himachalen-4-one thiosemicarbazone derivative with N-aryl-C-ethoxycarbonyl-nitrilimines and diarylnitrilimines via a 1,3-dipolar cycloaddition reaction. Materials & methods: The structures were confirmed by NMR, IR and high-resolution mass spectroscopy (HRMS). Results & conclusion: The newly synthesized hybrid compounds were tested for their in vitro antitumor activities against a panel of cancer cell lines including fibrosarcoma (HT-1080), lung carcinoma (A-549) and breast carcinoma (MCF-7 and MDA-MB-231). Among the tested products, 4a showed excellent activity against the HT-1080 and MCF-7 cell lines with IC 50 values of 11.18 ± 0.69 and 12.38 ± 0.63 μm, comparable to that of the reference drug. Docking results confirmed that the active inhibitors were well accumulated in the mushroom tyrosinase active site. Flow cytometry analysis indicated that hybrid 4a induced apoptosis and cell cycle arrest in the G 0 /G 1 phase. Molecular modeling studies affirmed the intercalative binding of compound 4a in the active site.

3-Acetylisoxazolines were synthesized by the reaction of natural (R)-limonene and (R)-carvone with acetone in the presence of iron (III) nitrate. The reaction showed to be highly peri- and regioselective. Next, using a 1,3-dipolar cycloaddition reaction, the mono-3-acylisoxazolines derived from these monoterpenes were evaluated for their reactivity with nitrilimines. Only the enone of carvone-isoxazoline was regioselectively reactive, providing a new fused isoxazoline-carvone-pyrazolines. The structure of all the newly synthesized mono-cycloadducts (3 & 5) and bis-cycloadducts (4 & 7a-c) were fully identified based on their HRMS and NMR spectral data. They have also been screened for their cytotoxic activity against four human cancer cell lines: fibrosarcoma (HT-1080), lung carcinoma (A-549), and breast (MCF-7 and MDA-MB-231) cell lines. The obtained results showed that compound 4 was a potent cytotoxic agent against all selected cells. The possible mechanism of apoptosis induction by compound 4 was investigated using Annexin-V binding assay, caspase-3/7 activity and analysis cell cycle progression. The compound 4 induced the early apoptosis of both MCF-7 and MDA-MB-231 through caspase-3/7 activation, and the compound 4 have elicited S and G2/M phase arrest in MCF-7and MDA-MB-231 cancer cells, respectively. For further target investigations, a molecular docking study was employed and it showed that compound 4 has an inhibitory activity against Pim-1 protein kinase. Molecular dynamics study showed that compound 4/Pim-1 complex was stable during the simulation run at different time intervals. In-Silico ADMET predicted that compound 4 has good pharmacokinetic properties with high estimated oral bioavailability., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

With recent advances in novel chemotherapeutic agents and increasing use of autologous hematopoietic stem cell transplant, there has been a significant improvement in outcomes for patients with AL Amyloidosis. Daratumumab, with its excellent safety and efficacy profile, appears to be an ideal treatment option for patients with newly diagnosed as well as relapsed refractory AL amyloidosis. In this systematic review, we analyzed the published literature on the role of Daratumumab in pretreated relapsed and refractory AL-amyloidosis patients using PubMed, Embase, Cochrane, and clinicaltrials.gov databases. A total of 16 studies evaluated the role of Daratumumab as monotherapy (DMT) or in combination with other chemotherapeutic agents (DCT). DMT and DCT were associated with promising efficacy with hematologic and organ responses (cardiac/renal) seen in 50%-90% and 50%-80% of the patients, respectively. Daratumumab appeared to be well tolerated with no significant treatment-related adverse events as DMT or DCT., (Copyright © 2021. Published by Elsevier Inc.)

Background: Resistance to cisplatin is a major obstacle to effective treatment of bladder cancer (BC). The present study aimed to determine whether a combination of acriflavine (ACF) with cisplatin could potentiate the antitumor property of cisplatin against the BC cells. Furthermore, the molecular mechanism behind the anticancer action of ACF was considered., Methods and Results: Two human BC cells (5637 and EJ138) contain mutated form of p53 was culture in standard condition. Cotreatment protocol (simultaneous combination of IC 30 value of ACF + various dose of cisplatin for 72 h) and pretreatment protocol (pretreatment with IC 15 value of ACF for 24 h + various dose of cisplatin for 48 h) was used to determine the effect of ACF on the cells' sensitivity to main drug cisplatin. To assess the mechanism of action of ACF, real-time PCR was used to evaluate mRNA levels of hypoxia-inducible factor-1α (HIF-1α), Bax, Bcl-2, topoisomerase1 (TOP1) and topoisomerase 2 (TOP2A). Combination of ACF with cisplatin either as cotreatment or opretreatment protocol could significantly reduce the IC 50 values of cisplatin as compared to the IC 50 of cisplatin when use as a single drug. In addition, ACF could markedly decrease mRNA expression of TOP1 and TOP2A without changing the expression of HIF-1ɑ, Bax and Bcl-2., Conclusions: Our findings indicate that combination of cisplatin with ACF was able to significantly enhance the sensitivity of BC cells to cisplatin. The antitumor activity of ACF is exerted through the downregulation of TOP1 and TOP2A genes expression. ACF may serve as an adjuvant to boost cisplatin-based chemotherapy., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)