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Abstract Ephedra is one of the many medicinal herbs that have been used as folk/traditional medicine in Jordan and other countries to cure various illnesses. Plants of this genus are well known for their antioxidant and antibacterial properties. In this study, three different solvents were used to obtain Ephedra extracts. When evaluated, the Ephedra alata Decne ethanolic extract reportedly had the greatest levels of total phenolic compounds (TPC) and total flavonoid compounds (TFC). The aqueous extracts displayed the highest antioxidant activity in the DPPH and ABTS assays, demonstrating their considerable capacity to neutralize free radicals. However, when evaluated using the FRAP method, the acetone extracts showed the strongest antioxidant activity, indicating their high reducing power. LC–MS/MS, a potent method of analysis that combines the liquid chromatographic separation properties with mass spectrometry detection and identification capabilities, was used in this study to detect and measure phytochemical content of a total of 24 phenolic compounds and 16 terpene compounds present in the extracts of Ephedra alata Decne. Various concentrations of these chemicals were found in these extracts. The extracts’ inhibitory effects on albumin denaturation and alpha-amylase activity were also assessed; the findings demonstrated the potentials of these extracts as anti-inflammatory and anti-diabetic medicines, with the acetone extract having the lowest IC50 values in the concomitant tests (306.45 µg/ml and 851.23 µg/ml, respectively). Furthermore, the lowest IC50 value (of 364.59 ± 0.45 µg/ml) for the 80% ethanol extract demonstrated that it has the strongest antiproliferative impact regarding the MDA-MB-231 breast cancer cell line. This finding indicates that this particular extract can be potentially used to treat cancer.

Breast cancer is the most recurrently identified and one of women’s prominent causes of death. Currently, researchers have turned their focus on natural chemicals from synthetic chemicals due to their environmental, economic, and health benefits. Considering this, the medicinal plant Leucas aspera was chosen for the current study. The aim of this study was to isolate and characterize secondary metabolites from L. aspera and determine the antiproliferative and antimigratory activities in the MDA-MB-231 cell line under in vitro conditions. Phytochemicals from L. aspera were isolated through sequential extraction using hexane, dichloromethane, and ethyl acetate. These extracts were qualitatively screened, subjected to FT-IR, and analyzed using GC-MS. The antiproliferative activity was determined through the MTT assay. Scratch assay was utilized to determine the antimigratory activity of the plant extracts. The phytochemical analysis revealed the presence of steroids, alkaloids, phenols, flavonoids, galactose, tannins, saponins, and amino acids in the extracts. The results of the cell viability assay indicated that the crude dichloromethane and ethyl acetate extracts inhibited cell proliferation, with inhibitory concentrations of 5 and 3 μg/ml, respectively. In contrast, the crude hexane extract did not exhibit any cytotoxicity. Furthermore, the scratch assay results showed that the plant extracts had cell migration inhibitory properties. The outcomes of the current study conclude that L. aspera possesses active therapeutic agents with strong anticancer potential, effectively impeding the proliferation and invasion of MDA-MB-231. Further studies are needed to identify the potential active agents that contribute to these activities.

Studies have shown that simulated microgravity (SMG) affects tumor cell growth and metastasis. However, the underlying molecular basis is still not known. In recent years, due to the high expression of CD44 in invasive basal breast tumors, it has been the subject of many studies. The aim of present study was to investigate the gene expression of CD44 in MDA-MB-231cell line of breast cancer in microgravity conditioncell line was proliferated under normal gravity and microgravity (1 and 3 days) using 2-D clinostat. Gene expression was measured using real-time PCR technique. SMG increased gene expression (100%) after 1 day and decreased it (15%) during 3 days in comparison to the control samples. It seems that the response of cancer cells to microgravity is time dependent and simulated microgravity treatment for 3 days may have a positive effect on cancer characteristics of MDA-MB-231 cell line in order to decrease the expression of CD44.

Abstract Background Pomegranate is known for its beneficial properties due to its high content in antioxidants and might constitute a natural option for preventing and treatment of different pathologies including cancer. Since mitochondria are involved in tumorigenesis through ROS production and modulation of oxidative metabolism, we investigated the biological effects of pomegranate on cellular redox state, proliferation and metabolism in the breast cancer cell line MDA-MB-231 (MDA). Methods MDA were treated for 24 h with graded concentration of filtered Pomegranate juice (PJ) and tested for metabolic Flux Analysis with XFe96 Extracellular Flux Analyzer, for proliferation using the xCELLigence System Real-Time Cell Analyzer and for intracellular ROS content by Confocal Microscopy Imaging. Results Cells-treatment with freshly prepared pomegranate juice (PJ) resulted in a significant reduction of the intracellular ROS content already at the lower concentration of PJ tested. Additionally, it enhanced mitochondria respiration, and decreased glycolysis at high concentrations, inhibiting at the same time cell proliferation. As pomegranate is a seasonal fruit, assessment of optimum storage conditions preserving its bio-active properties was investigated. Our results indicated that storage conditions under controlled atmosphere for 30 days was able to enhance mitochondrial respiration at the same extent than freshly extracted PJ. Conversely, freezing procedure, though retaining the antioxidant and cell-growth inhibitory property, elicited an opposite effect on the metabolic profile as compared with fresh extract. Conclusion Overall, the results of our study, on the one hand, confirms the preventive/therapeutic potential of PJ, as well as of its post-harvested processing, for cancer management. On the other hand, it highlights the intrinsic difficulties in attaining mechanistic insights when a multiplicity of effects is elicited by a crude mixture of bio-active compounds.

Tomasz Kostrzewa,1 Izabela Nowak,2 Agnieszka Feliczak-Guzik,2 Joanna Drzeżdżon,3 Dagmara Jacewicz,3 Magdalena Górska-Ponikowska,1,4,5 Alicja Kuban-Jankowska1 1Department of Medical Chemistry, Faculty of Medicine, Medical University of Gdansk, Gdansk, 80-211, Poland; 2Department of Applied Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Poznań, 61-614, Poland; 3Department of Environmental Technology, Faculty of Chemistry, University of Gdansk, Gdansk, 80-308, Poland; 4IEMEST Istituto Euro-Mediterraneo di Scienza e Tecnologia, Palermo, 90127, Italy; 5Department of Biophysics, Institute of Biomaterials and Biomolecular Systems, University of Stuttgart, Stuttgart, 70174, GermanyCorrespondence: Tomasz Kostrzewa; Alicja Kuban-Jankowska, Department of Medical Chemistry, Faculty of Medicine, Medical University of Gdansk, Gdansk, 80-211, Poland, Tel +48 58 349 14 50, Fax +48 58 349 14 56, Email tomasz.kostrzewa@gumed.edu.pl; alicja.kuban-jankowska@gumed.edu.plIntroduction: Solid lipid nanoparticles (SLN) have been considered lately as promising drug delivery system in treatment of many human diseases including cancers. We previously studied potential drug compounds that were effective inhibitors of PTP1B phosphatase – possible target for breast cancer treatment. Based on our studies, two complexes were selected for encapsulation into the SLNs, the compound 1 ([VO(dipic)(dmbipy)] · 2 H2O) and compound 2 ([VOO(dipic)](2-phepyH) · H2O). Here, we investigate the effect of encapsulation of those compounds on cell cytotoxicity against MDA-MB-231 breast cancer cell line. The study also included the stability evaluation of the obtained nanocarriers with incorporated active substances and characterization of their lipid matrix. Moreover, the cell cytotoxicity studies against the MDA-MB-231 breast cancer cell line in comparison and in combination with vincristine have been performed. Wound healing assay was carried out to observe cell migration rate.Methods: The properties of the SLNs such as particle size, zeta potential (ZP), and polydispersity index (PDI) were investigated. The morphology of SLNs was observed by scanning electron microscopy (SEM), while the crystallinity of the lipid particles was analyzed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The cell cytotoxicity of complexes and their encapsulated forms was carried out against MDA-MB-231 breast cancer cell line using standard MTT protocols. The wound healing assay was performed using live imaging microscopy.Results: SLNs with a mean size of 160 ± 25 nm, a ZP of − 34.00 ± 0.5, and a polydispersity index of 30 ± 5% were obtained. Encapsulated forms of compounds showed significantly higher cytotoxicity also in co-incubation with vincristine. Moreover, our research shows that the best compound was complex 2 encapsulated into lipid nanoparticles.Conclusion: We observed that encapsulation of studied complexes into SLNs increases their cell cytotoxicity against MDA-MB-231 cell line and enhanced the effect of vincristine.Keywords: solid lipid nanoparticles, stability of nanoparticles, oxovanadium(IV) and dioxovanadium(V) complexes, triple-negative MDA-MB-231 breast cancer cell line, live imaging microscopy

Breast cancer has been recorded as a frequent malignant cancer. The side effects of current chemotherapy drugs are still a severe problem. Hence, naturally occurring phytochemicals can be a possible solution to overcome this issue. Therefore, naturally occurring hyperforin was used to assess its anticancer effect against triple-negative breast cancer cells (MDA-MB-231) and its effectiveness against taxol (clinically used drug). Both compounds’ anticancer activity and mechanism of action were evaluated by analysing various approaches such as ELISA, flow cytometry and PCR microarray. Our results showed a lower IC50 of hyperforin (7.18 µg/mL) compared to taxol (7.91 µg/mL, P

Objective(s): Cerium oxide nanoparticles (Ceo2 NPs) are considered one of the most effective nanomaterials for drug delivery. The current study aimed to investigate the anticancer activities of doxorubicin-loaded Ceo2 NPs (DOX-Ceo2 NPs) against the MDA-MB-231 human breast cancer cell line. Materials and Methods: Ceo2 NPs were synthesized using the GREEN synthesis method and loaded with DOX (DOX-Ceo2 NPs). The physicochemical properties of the Ceo2 NPs were evaluated using FTIR, XRD, DLS, zeta potential, and electron microscopy (SEM/TEM). Cultured MDA-MB-231 cells were treated with different concentrations of bare Ceo2 NPs, free DOX, and DOX-Ceo2 NPs. In addition, HDF cells were treated with different concentrations of Ceo2 NPs. MTT, wound healing, and flow cytometry assays were performed to determine the cell viability, migration, and apoptosis, respectively. qPCR was performed to investigate the expression of genes involved in apoptosis, including caspase (CASP) 3, 8, 9, and Bcl-2. Results: The XRD and FTIR results confirmed the synthesis of pure and crystalline structured-Ceo2 NPs. The average size, PDI, and zeta potential of the Ceo2 NPs were approximately 239.1 nm, 0.074, and -9.04 mV, respectively. In vitro assays showed that DOX-Ceo2 NPs exhibited higher cell proliferation inhibition, migration suppression, and apoptosis induction through the upregulation of CASP3, CASP8, and CASP9 genes and downregulation of Bcl-2. Conclusion: Our data demonstrate the potential of Ceo2 NPs for the efficient delivery of DOX and, subsequently, the improvement of its anticancer activities. Therefore, DOX-Ceo2 NPs have the potential to be proposed as promising anticancer agents for breast cancer. [ABSTRACT FROM AUTHOR]

In this article, we have reported the synthesis and structural characterization of complexes containing Co(III), Cu(II), Zn(II), and Hg(II) metal cations. The ligand potassium azepane-1-carbodithioate (acdt) behaves as a monodentate and bidentate and forms complexes with the metals mentioned above. We investigated the electronic and emission spectra of the ligand potassium azepane-1-carbodithioate (acdt) and its metal complexes [Co(acdt)3]·CHCl3 (1), [Cu(acdt)2] (2), [Zn2(μ2-acdt)2(acdt)2] (3), and [PhHg(acdt)] (4). A photoluminescence study was also carried out and the results revealed that all compounds are fluorescent. Furthermore, this synthesized ligand and its complexes are passed through to examine their cytotoxic activity against human breast cancer cell line MDA-MB-231 and results suggested that complex [Co(acdt)3]·CHCl3 has sufficiently better activity than others. Furthermore, we have explored the impact of the synthesized ligand and its transition metal complexes on glucose metabolism within the human breast cancer cell line MDA-MB-231. Inhibiting glucose uptake can induce starvation in cancer cells, potentially resulting in cell death due to energy deprivation. Our results indicate that the Co(III) complex-treated group exhibited a greater inhibition of glucose uptake compared to groups treated with ligands and other metal complexes such as Cu, Zn, and Hg. Furthermore, we also measured the extracellular NO level in the ligand and its metal complexes of Co(III), Cu(II), Zn(II), and Hg(II) treated MDA-MB-231 cells and results indicated that the free ligand and its metal complexes induced the production of nitric oxide in MDA-MB-231 cells. Among the four metal complexes, Co-complex 1 elevated the nitric oxide level in MDA-MB-231 cells to 75.91 μM. In contrast, the groups treated with the complexes of Cu(II) (2), Zn(III) (3), and Hg(II) (4) induced NO levels of 62.91, 49.24, and 33.10 μM, respectively. This suggests that complex 1 induces nitric oxide production and enhances oxidative stress in MDA-MB-231 cells more significantly compared to the groups treated with the free ligand as well as with metal complexes 2–4. Overall, the data strongly suggest that complex 1 exhibits significant anticancer activity against the human breast cancer cell line MDA-MB-231, making it a promising candidate for combating breast cancer progression. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is known to be one of the most prevalent malignancies in women worldwide. Umbelliprenin (UMB) is a naturally-occurring component derived from plant species, which has shown anticancer properties. The present study aimed to evaluate the effect of UMB on the PI3K / Akt / ERK signaling pathway and their products HIF-1α / VEGF in the MDA-MB-231 cell line. Method: In this experimental study, the cytotoxic effect of UMB on MDA-MB- 231 cells was evaluated using the MTT assay and the UMB concentrations of IC5 and IC10 were selected for the signaling pathway study. MDA-MB-231 cells were stimulated with EGF and CoCl2 and UMB IC5 and IC10 effects on gene expression and translation was studied. PI3K / Akt / mTOR / S6K / Erk1 and 2 / 4E-BP1 / HIF-1α / HIF-1α/ EGFR / VEGFR and VEGF mRNA expression, and VEGF / HIF-1α proteins were evaluated employing real time polymerase chain reaction and western blot analysis, respectively. Results: The concentrations of UMB in IC10 and IC5 were 20 and 10 μM, respectively. UMB, specifically IC10, significantly inhibited PI3K, ERK1, ERK2, Akt, mTOR, HIF1-α, HIF1-β mRNA, as well as HIF-1α and VEGF protein expression. Conclusion: Our results suggested that UMB, a cytotoxic agent, inhibits PI3K / Akt / ERK signal pathway in the CoCl2 or EGF-stimulated MDA-MB-231 cells.

Introduction: Chelidonine, a bio-active component of Chelidonium majus, has been investigated for its anti-proliferative effects on various cancer cell lines with multidrug resistance (MDR). Although the results are auspicious, its poor water solubility and low bioavailability are the main limitations for clinical applications. This study aimed to develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with chelidonine, in order to enhance its bioavailability for oral administration and improve the therapeutic index. Methods: Herein, we encapsulated chelidonine in PLGA nanoparticles using a single emulsion solvent evaporation method. Nanoparticles were characterized in terms of size, surface charge and morphology, encapsulation efficiency, drug loading, and in vitro drug release profile. The anti-cancer efficacy of chelidonine-loaded nanoparticles and free chelidonine was evaluated in MDA-MB-231 breast cancer cells. Results: The physicochemical characteristics showed spherical particles in nanometer size range (263 ± 19.6 nm), with negative surface charge (−20.67 ± 2.48 mv), high encapsulation efficiency (76.53 ± 3.61%), and drug loading (22.47 ± 0.09%), as well as drug release amount of 60.27±5.68% up to 10 days. Furthermore, chelidonine-loaded nanoformulations were found to improve anti-cancer potential, compared with unentrapped chelidonine. Conclusion: This in vitro study showed that the encapsulation of chelidonine, as a potent herbal drug, in a polymeric matrix enhances its bioavailability. This offers an efficient vehicle for targeted drug delivery in cancer treatment.

Breast cancer has been recorded as a frequent malignant cancer. The side effects of current chemotherapy drugs are still a severe problem. Hence, naturally occurring phytochemicals can be a possible solution to overcome this issue. Therefore, naturally occurring hyperforin was used to assess its anticancer effect against triple-negative breast cancer cells (MDA-MB-231) and its effectiveness against taxol (clinically used drug). Both compounds' anticancer activity and mechanism of action were evaluated by analysing various approaches such as ELISA, flow cytometry and PCR microarray. Our results showed a lower IC50 of hyperforin (7.18 µg/mL) compared to taxol (7.91 µg/mL, P < 0.05) and hyperforin has almost similar anticancer effects as taxol against MDA-MB-231 cells. PCR microarray results showed that hyperforin induced the expression of caspases activator leading to a caspases-dependent cell death pathway whereas taxol uses TNF-mediated cell death. The results suggest that hyperforin may act as a good cell death-inducing agent. ABBREVIATIONS: TNBC: Triple negative breast cancer; DNA: Deoxyribonucleic acid; RNA: Ribonucleic acid; ROS: Reactive oxygen species; 5-FU: Fluorouracil; TRAIL: TNF-related apoptosis-inducing ligand; AKT: Protein kinase B; COX-2: Cyclooxygenase-2; PCR: Polymerase chain reaction; Bax: Bcl-2-associated X protein; BCL-2: B-cell lymphoma 2; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; mRNA: Messenger ribonucleic acid; MCL1: Myeloid-cell leukemia 1; LDH: Lactate dehydrogenase; ELISA: Enzyme-linked immunosorbent assay; MMP: Mitochondrial membrane potential; MCP-1: Monocyte chemoattractant protein-1; ATCC: American Type Culture Collection; RPMI: Roswell Park Memorial Institute; XIAP: X-linked inhibitor of apoptosis protein; FBS: Fetal bovine serum; MCL-1: Myeloid-cell leukemia 1; DMEM: Dulbecco's Modified Eagle Medium; DMSO: Dimethyl sulfoxide; CASP3: Caspase 3; RPMI: Roswell Park Memorial Institute; DMEM: Dulbecco's Modified Eagle Medium; FBS: Fetal bovine serum; h: Hour; TNF-α: Tumour necrosis factor alpha; P53: Tumor protein P53; min: Minutes; cps: Count presecond; OD: Optical density; rpm: Revolutions per minute; PI: Propidium iodide; SD: Standard deviation; DDR: Death Domoin Receptor; TRADD: Tumor necrosis factor receptor type 1-associated DEATH domain; HRK: Harakiri, BCL2 Interacting Protein; RIPK2: Receptor-interacting serine/threonine-protein kinase 2; BIK: BCL2 interacting killer; DCF: 2', 7' –dichlorofluorescein; DCF-DA: Dichlorofluorescin Diacetate; FADD: Fas Associated Via Death Domain; TNFRSF: Tumor necrosis factor receptor superfamily; FITC: Fluorescein isothiocyanate; DMSO: Dimethyl sulfoxide; CFLAR: CASP8 And FADD Like Apoptosis Regulator; BID: BH3-interacting domain death agonist; BIRC: Baculoviral IAP repeat-containing protein; CIDEA: Cell death activator CIDE-A; CIDEB: Cell Death Inducing DFFA Like Effector B; BrdU: Bromodeoxyuridine; RFU: Relative fluorescence unit; NF-kB: Nuclear Factor kappa-light-chain-enhancer of activated B cells; %: Percentage; µL: microliter; µM: Micromolar; °C: degree Celcius; ng/mL: Nanograms per millimeter; mg/mL: Milligrams per milliliter; µg/mL: Micrograms per milliliter; ΔΨm: Mitochondrial membrane potential; TNFα: Tumour necrosis factor α; Bcl-xL: B-cell lymphoma-extra large; MDR1: Multidrug Resistance Mutation; AIB1: Amplified in breast cancer 1; LTBR: Lymphotoxin Beta Receptor Highlights Utilization of hyperforin as anticancer agent against triple negative breast cancer. Hyperforin exhibited a lower IC50 compared to taxol in inhibiting growth of MDA-MB-231 cells. Hyperforin shows similar potential anticancer activity as taxol. Hyperforin uses mitochondrial death pathway to induce cell death in MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the anticancer activity of methanolic extract of Illicium verum against triple-negative breast cancer MDA-MB-231 cell line. Methods: A cell culture experimental study was carried out at Pharmacology department of Bahria University Medical and Dental College (January to June 2021) in collaboration with Aga Khan University, Karachi, Pakistan. Cell viability and proliferation assays were used to quantify dead and alive cells by utilizing a tetrazolium assay and an enzyme immunosorbent plate reader was used to calculate their absorbance. For the apoptosis initiation assay, these cells were dyed with a fluorescent stain and observed for fluorescence and apoptosis. During cell viability testing, various I. verum methanolic extract doses (0.125, 0.25, 0.5, 1, 3, 6, 12, and 25µg/ml) were employed to treat MDA-MB-231 cells, while the IC50 dose of 2.8µg/ml was used for both the cell proliferation and apoptosis initiation assays. Results: In the cell viability assay, all I. verum methanolic extract doses exhibited a substantial decrease in the viability of MDA-MB-231 cells (less than 0.01 p-value). In cell proliferation assay and apoptosis initiation, the IC50 dose of 2.8µg/ml of I. verum methanolic extract also exhibited a substantial decrease in cell division (less than 0.01 p-value) and the initiation of apoptosis in MDA-MB-231 cells. Conclusion: Illicium verum methanolic extract have strong anticancer activity against triple-negative breast cancer MDA-MB-231 cell line through cytotoxicity, proliferation reduction, and apoptosis initiation mechanisms. [ABSTRACT FROM AUTHOR]

Aim:It was aimed to investigate the effect of miR-34a-5p and miR-145-5p on breast cancer cell line MDA-MB-231 and to determine the expression of target genes of these microRNAs (miRNAs).Materials and Methods:Firstly, literature search and in silico analysis were performed to detect possible target genes of miR-34a-5p and miR-145-5p, which are known to be tumor suppressors. Mimic miR-34a-5p and miR-145-5p were transfected to the breast cancer cell line MDA-MB-231. Deregulated genes were investigated by the quantitative real-time polymerase chain reaction compared to control cells. Also, the effect of these miRNAs on proliferation was determined using the Water Soluble Tetrazolium Salt-8 method. Finally, the expressions of epithelial mesenchymal transition (EMT) markers, which are known to be important in the metastatic process, are examined.Results:The proliferation of the miR-34a-5p or miR-145-5p transfected cells decreased compared to the control groups. The expression of E2F transcription factor 1 (E2F1) (p=0.009), mitogen activated protein kinase 1 (MEK1) (p=0.001) and cyclin dependent kinase 4 (CDK4) (p=0.005) genes, which were among the genes targeted by miR-34a-5p, were significantly reduced. EMT markers were significantly changed in miR-34a-5p transfected cells (E-Cad increase p=0.01; Vimentin decrease p=0.008). Kruppel-like factor 4 (KLF4) (p=0.007) targeted miR-145-5p were significantly reduced and EMT markers were significantly changed in miR-145-5p transfected cells (E-Cad increase p=0.0005; Vimentin decrease p=0.006).Conclusion:miR-34a-5p and miR-145-5p may have an impact on the breast cancer cell line MDA-MB-231 proliferation and EMT mechanism. At the same time, according to our study results, it was revealed that E2F1, MEK1 and CDK4 genes, whose expression level decreased after transfection of mimic miR-34a-5p, could be targeted by miR-34a-5p in breast cancer, and that the expression level of KLF4, which decreased as a result of mimic miR-145-5p transfection, could be the target.

Abstract Background The human SH3 domain Binding Glutamic acid Rich Like 3 (SH3BGRL3) gene is highly conserved in phylogeny and widely expressed in human tissues. However, its function is largely undetermined. The protein was found to be overexpressed in several tumors, and recent work suggested a possible relationship with EGFR family members. We aimed at further highlighting on these issues and investigated SH3BGRL3 molecular interactions and its role in cellular migration ability. Results We first engineered the ErbB2-overexpressing SKBR3 cells to express exogenous SH3BGRL3, as well as wild type Myo1c or different deletion mutants. Confocal microscopy analysis indicated that SH3BGRL3 co-localized with Myo1c and ErbB2 at plasma membranes. However, co-immunoprecipitation assays and mass spectrometry demonstrated that SH3BGRL3 did not directly bind ErbB2, but specifically recognized Myo1c, on its IQ-bearing neck region. Importantly, the interaction with Myo1c was Ca2+-dependent. A role for SH3BGRL3 in cell migration was also assessed, as RNA interference of SH3BGRL3 in MDA-MB-231 cells, used as a classical migration model, remarkably impaired the migration ability of these cells. On the other side, its over-expression increased cell motility. Conclusion The results of this study provide insights for the formulation of novel hypotheses on the putative role of SH3BGRL3 protein in the regulation of myosin-cytoskeleton dialog and in cell migration. It could be envisaged the SH3BGRL3-Myo1c interaction as a regulation mechanism for cytoskeleton dynamics. It is well known that, at low Ca2+ concentrations, the IQ domains of Myo1c are bound by calmodulin. Here we found that binding of Myo1c to SH3BGRL3 requires instead the presence of Ca2+. Thus, it could be hypothesized that Myo1c conformation may be modulated by Ca2+-driven mechanisms that involve alternative binding by calmodulin or SH3BGRL3, for the regulation of cytoskeletal activity.

Background: Triple-negative breast cancer has the poorest prognosis and survival rates compared to other breast cancer subtypes due to its invasive behaviours. This type of cancer does not respond to biological therapies and exhibits resistance to available treatment options. Therefore, it is imperative to discover new therapeutics to address this challenge., Methods: In this study, a TNBC cell line was utilized to investigate the anti-metastatic effect of crocin on the Wnt/β-catenin pathway. Cell proliferation was assessed using the MTT assay, and the effects of crocin on migration were monitored through transwell and wound healing experiments. The expression of specific epithelial-mesenchymal transition marker genes was evaluated using real-time polymerase chain reaction, and β-catenin expression was also examined through real-time polymerase chain reaction., Results: The findings revealed that crocin significantly inhibits cell proliferation and migration of tumour cells in a dose-dependent manner. Moreover, crocin decreased the expression of Vimentin, Snail, Zeb-1, and β-catenin. Additionally, crocin increased the expression of E-cadherin in the MDA-MB-231 cell line., Conclusions: The results demonstrated an association between crocin and the Wnt/β-catenin signalling pathway. In conclusion, this study establishes that crocin holds promise as a potential therapeutic option for triple-negative breast cancer., Competing Interests: The authors declare there is no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Protein-drug interactions are crucial for understanding drug delivery and cell functions. Jacalin is a suitable molecule for such targeting, as it specifically recognizes the tumor-associated Thomsen-Friedenreich (TF) antigen that is expressed on the glycosylated proteins in cancer cells. The present paper describes the interaction of curcumin and jacalin, a possible carrier molecule for the delivery of antitumor drugs due to its ability to recognize tumor cells. Our results have shown that both steady-state fluorescence and fluorescent labelling of jacalin are two reliable methods to determine jacalin-curcumin interactions. The affinity of jacalin for curcumin is consistently within the micromolar range (using fluorescence and microscale thermophoresis) showing high-affinity binding of the complex. In vitro experiments on triple-negative breast cancer MDA-MB-231 cells indicated inhibition of cell growth after treating with the jacalin-curcumin complex for 48 h. The cell survival fraction was significantly reduced to 50% after combined treatment. In this paper, we report for the first time about the jacalin-curcumin interaction. We quantified this unique biomolecular interaction and gathered additional information on the binding event. We observed that the jacalin-curcumin complex inhibits the proliferation of the triple-negative breast cancer MDA-MB-231 cells.

Abstract Background Cancer of the breast is known to be among the top spreading diseases on the globe. Triple-negative breast cancer is painstaking the most destructive type of mammary tumor because it spreads faster to other parts of the body, with high chances of early relapse and mortality. This research would aim at utilizing computational methods like quantitative structure–activity relationship (QSAR), performing molecular docking studies and again to further design new effective molecules using the QSAR model parameters and to analyze the pharmacokinetics “drug-likeliness” properties of the new compounds before they could proceed to pre-clinical trials. Results The QSAR model of the derivatives was highly robust as it also conforms to the least minimum requirement for QSAR model from the statistical assessments of (R 2) = 0.6715, (R 2 adj) = 0.61920, (Q 2) = 0.5460 and (R 2pred) of 0.5304, and the model parameters (AATS6i and VR1_Dze) were used in designing new derivative compounds with higher potency. The molecular docking studies between the derivative compounds and Maternal Embryonic Leucine Zipper Kinase (MELK) protein target revealed that ligand 2, 9 and 17 had the highest binding affinities of − 9.3, − 9.3 and − 8.9 kcal/mol which was found to be higher than the standard drug adriamycin with − 7.8 kcal/mol. The pharmacokinetics analysis carried out on the newly designed compounds revealed that all the compounds passed the drug-likeness test and also the Lipinski rule of five. Conclusions The results obtained from the QSAR mathematical model of parthenolide derivatives were used in designing new derivatives compounds that were more effective and potent. The molecular docking result of parthenolide derivatives showed that compounds 2, 9 and 17 had higher docking scores than the standard drug adriamycin. The compounds would serve as the most promising inhibitors (MELK). Furthermore, the pharmacokinetics analysis carried out on the newly designed compounds revealed that all the compounds passed the drug-likeness test (ADME and other physicochemical properties) and they also adhered to the Lipinski rule of five. This gives a great breakthrough in medicine in finding the cure to triple-negative breast cancer (MBA-MD-231 cell line).

Objective(s): Breast cancer is one of the most common types of cancer. Chemotherapeutic agents used during treatment induce cytotoxic effects also on normal cells in the tissues. Anti-oxidants used in combination with chemotherapeutic agents have been shown to reduce toxicity on normal cells to a minimum, and some anti-oxidant substances have chemotherapeutic effects. Cisplatin (CDDP) is a platinum class drug that is used clinically in the treatment of many cancers. Resveratrol (RSV) is a natural polyphenol with potent anti-oxidant and anticancer properties. In this study, we aimed to investigate apoptotic effects of using cisplatin and RSV alone or in combined treatment of MDA-MB-231 cells.Materials and Methods: The cytotoxic effects of the drugs on MDA-MB-231 cells were determined by MTT method. Subsequently, the change in CDDP-induced apoptotic effect after RSV addition was examined using the AnnexinV FITC labeling, and TUNEL staining method. Activation of caspase-9, -3 in MDA-MB-231 cells was measured by flow cytometer. The mitochondrial membrane potential (MMP), the major factor on the intrinsic pathway, was measured using flowcytometry. Results: The combined dose (23 μM CDDP + 72 μM RSV) produced more cytotoxicity than the agents used alone, leading to early apoptosis (8.2%), 31% depolarization, and 23% DNA fragmentation. Caspase-9 was found to be 30.5% in this combined group and caspase-3 was 26.3%. Conclusion: RSV, an effective anti-oxidant, and CDDP as an effective drug in cancer treatment, were found to increase apoptosis when given in the MDA-MB-231 cell.

A biosurfactant producing bacterium was identified as Pseudomonas aeruginosa DNM50 based on molecular characterization (NCBI accession no. MK351591). Structural characterization using MALDI-TOF revealed the presence of 12 different congeners of rhamnolipid such as Rha-C8-C8:1, Rha-C10-C8:1, Rha-C10-C10, Rha-C10-C12:1, Rha-C16:1, Rha-C16, Rha-C17:1, Rha-Rha-C10:1-C10:1, Rha-Rha-C10-C12, Rha-Rha-C10-C8, Rha-Rha-C10-C8:1, and Rha-Rha-C8-C8. The radical scavenging activity of rhamnolipid (DNM50RL) was determined by 2, 3-diphenyl-1-picrylhydrazyl (DPPH) assay which showed an IC50 value of 101.8 μg/ ml. The cytotoxic activity was investigated against MDA-MB-231 breast cancer cell line by MTT (4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide) assay which showed a very low IC50 of 0.05 μg/ ml at 72 h of treatment. Further, its activity was confirmed by resazurin and trypan blue assay with IC50 values of 0.01 μg/ml and 0.64 μg/ ml at 72 h of treatment, respectively. Thus, the DNM50RL would play a vital role in the treatment of breast cancer targeting inhibition of p38MAPK.