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Plants play an important role in nanoparticle preparation because they are easily accessible, environmentally friendly, and inexpensive. In this study, we used an ethanolic extract of Mangifera indica seed as a reducing and stabilising agent to create zinc oxide (ZnO) nanoparticles (NPs). The ZnO NPs were examined using characterization techniques such as UV-Vis, Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The interaction of phytochemical constituents from plant extracts providing the biological reduction of zinc metal ions to ZnO had been identified by the UV-visible absorption studies. According to the FT-IR results, metal oxides exhibited interatomic vibration-driven absorption in the fingerprint area below 1000 cm–1. Particles appeared to be crystalline and also a rice-grain shape of ZnO NPs was confirmed by XRD, SEM, and TEM, respectively. In addition, the cytotoxic effect of ZnO NPs was checked using the SKMEL-28 cell line, showing an IC50 value of 32.686 μg/mL in the SKMEL-28 cell line, and 49.011 μg/mL in the typical L6 cell line. Furthermore, the synthesized NPs were subjected to (AO/EB) double staining approach to examine the apoptotic activity. The acridine orange/ethidium bromide method made strong evidence for demonstrating chromatin condensation and membrane blebbing. [ABSTRACT FROM AUTHOR]

In recent years, the development of green multifunctional nanoformulations with specific anticancer activity has gained importance among scientists. In the present study, Camelia sinensis extract/CuO nanoparticles (CSE/CuO NPs) and cisplatin (Cis)-loaded CSE/CuO NPs were prepared and characterized by various TEM, XRD, FTIR, and UV-Vis techniques. The antioxidant properties of the green CSE/CuO NPs were evaluated using the CUPRIC Reducing Antioxidant Capacity (CUPRAC) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS)/HRP methods. The drug release profile of the NPs was studied at pH 7.4 and pH 5.5. Additionally, the cytotoxic effects of CSE/CuO NPs and Cis-loaded CSE/CuO NPs on MIA-PaCa-2 pancreatic cancer were evaluated using the MTT assay and compared with normal HUVEC cells. Subsequently, the apoptotic activity of CSE/CuO NPs and Cis-loaded CSE/CuO NPs on MIA-PaCa-2 cells was evaluated using Annexin-V FITC, and their effects on multi-drug resistance were determined using the ABCG2 antibody by flow cytometric analysis. Our results showed that Cis-loaded CSE/CuO NPs exhibited a pH-sensitive drug release profile. CSE/CuO NPs were highly cytotoxic to MIA-PaCa-2 pancreatic cancer cells, while exhibiting very low cytotoxicity to HUVEC cells. Moreover, CSE/CuO NPs and Cis-loaded CSE/CuO NPs were found to have higher apoptotic activity and lower drug resistance compared to free Cis. Although many studies have been conducted with CSE, this study was the first to show that CSE/CuO NPs were dominantly and selectively effective against pancreatic cancer, and resistance to Cis and its side effects could be significantly reduced by CSE-derived nanocarriers. Additionally, for the first time, the antioxidant property was investigated by applying CUPRAC and ABTS methods. [ABSTRACT FROM AUTHOR]

Quetiapine (QTP) has been known to suppress cancer progression in patients suffering from mental disorders. This study aimed to produce the folate-linked chitosan-coated quetiapine/BSA nano-carriers (FCQB-NCs) and evaluate their antioxidant, apoptotic, and anti-metastatic potentials on prostate, pancreas, colon, and breast cancer cell lines. The FCQB-NCs were designed, produced, and characterized using DLS, FESEM, FTIR, and Zeta potential techniques. The nano-carriers antioxidant activity was studied by applying ABTS, DPPH, and FRAP assays. The FCQB-NCs' cytotoxicity and apoptotic/metastatic properties were evaluated utilizing MTT assay and qPCR-based analysis for measuring the apoptotic (Nf-KB)/metastatic (MMP2, MMP9, and MMP13) gene expression, respectively. The AO/PI fluorescent cell staining, DAPI staining, and scratch assay methods were conducted to verify the apoptotic and anti-metastatic activities of FCQB-NCs. The 51-nm FCQB-NCs (PDI = 0.26) exhibited antioxidant activity and selectively decreased the MDA-MB-231 cancer cells' viability by inducing Nf-KB overexpression, which caused the apoptosis pathway activation. Moreover, the FCQB-NCs suppressed the MDA-MB-231 cells' metastatic activity by down-regulating the MMP2, MMP9, and MMP13 gene expression, verified by detecting the decreased migration rate. The FCQB-NCs selectively induced apoptosis and suppressed metastasis in the human breast cancer cell line, which can be attributed to the stepwise release of QTP in two primary (extra-cellular release) and secondary (intra-cellular release) phases. The efficient selective cytotoxic impact of FCQB-NCs can be due to the novel stepwise release mechanism of the FCQB-NCs based on the two-phase entrapment of QTP by BSA and chitosan molecules. Therefore, FCQB-NCs have the potential to be used as an efficient selective anti-breast cancer. [ABSTRACT FROM AUTHOR]

Applying nanotechnology to design drug delivery systems is a promising turning point in cancer treatment strategies. In the current study, Lawson, a nonpolar anticancer phytochemical, was entrapped into β-cyclodextrin polymer to evaluate its selective cytotoxicity in several types of human cancer cell lines including MCF-7, AGS, A549, and PC3. The Lawson-loaded β-cyclodextrin nanocarriers (LB-NCs) were produced by applying a high-energy ultrasound-mediated homogenization technique. The LB-NCs were characterized by applying dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential, and field emission scanning electron microscopy (FESEM) analysis. Also, the selective cytotoxic impact of the LB-NCs was studied by conducting the MTT assay on human MCF-7, AGS, A549, and PC3 cancer cell lines. Finally, the type of cellular death was evaluated by measuring the cell cycle status and apoptotic gene expression profile of the treated MCF-7 cells by conducting flow cytometry and Q-PCR methods, respectively. The synthesized negatively charged (− 23.8 mV) nanoparticles (348.12 nm) exhibited apoptotic activity in the human breast MCF-7 cancer cells by upregulating the apoptotic gene expression profile (Caspase 3, 8, and 9). The LB-NCs exhibited a significant selective cytotoxic effect on the human cancer cell lines compared with the normal HUVEC cells. However, variable toxic intensities were detected depending on the cancer cell type. Selective cancer cell-depended anticancer activity of the produced LB-NCs has the potential to be considered their safe efficient targeted anticancer activity. However, studying the animal cancer models has to be conducted to verify their selective toxicity and clarify the cellular death mechanism. [ABSTRACT FROM AUTHOR]

Abstract The starting compound 3-amino-1,7-dihydro-4H-pyrazolo[4,3-c]pyridine-4,6(5H)-dione (1) is reacted with each of diketone and β-ketoester, forming pyridopyrazolo[1,5-a]pyrimidines 4a,b and 14a,b, respectively. The compounds 4 and 14 reacted with each of aromatic aldehyde and arenediazonium salt to give the respective arylidenes and arylhydrazo derivatives, respectively. The structure of the new products was established using spectroscopic techniques. The cytotoxic activity of selected targets was tested in vitro against three cancer cell lines MCF7, HepG2 and HCT116. The data obtained from enzymatic assays of TrKA indicated that compounds 7b and 16c have the strongest inhibitory effects on TrKA with IC50 = 0.064 ± 0.0037 μg/ml and IC50 = 0.047 ± 0.0027 μg/ml, respectively, compared to the standard drug Larotrectinib with IC50 = 0.034 ± 0.0021 μg/ml for the HepG2 cancer cell line. In cell cycle analysis, compounds 7b, 15b, 16a and 16c caused the greatest arrest in cell cycle at the G2/M phase. In addition, compound 15b has a higher apoptosis-inducing effect (36.72%) than compounds 7b (34.70%), 16a (21.14) and 16c (26.54%). Compounds 7b, 16a and 16c were shown fit tightly into the active site of the TrKA kinase crystal structure (PDB: 5H3Q). Also, ADME study was performed on some selected potent anticancer compounds described in this study.

Phenothiazine derivatives are widely studied in various fields such as biology, chemistry, and medicine research because of their pharmaceutical effects. The first compound used successfully in the treatment of psychosis was a phenthiazine derivative, chlorpromazine. Apart from its activity in neurons, chlorpromazine has also been reported to display anticancer and antibacterial properties. In this study, we present the synthesis and research on the activity of A549, MDA, MiaPaCa, PC3, and HCT116 cancer cell lines and of S. aureus, S. epidermidis, E. coli, and P. aeruginosa bacterial strains against a series of new tetracyclic chlorpromazine analogues containing a quinoline scaffold in their structure instead of the benzene ring and various substituents at the thiazine nitrogen. The structure of these novel molecules has been determined by 1H NMR, 13C NMR, and HRMS spectral techniques. The seven most active of the twenty-four new chlorpromazine analogues tested were selected to study the mechanism of cytotoxic action. Their ability to induce apoptosis or necrosis in cancer cells was assessed by flow cytometry analysis. The results obtained confirmed the proapoptotic activity of selected compounds, especially in terms of inducing late apoptosis or necrosis in cancer cell lines A549, MiaPaCa-2, and HCT-116. Furthermore, studies on the induction of cell cycle arrest suggest that the new chlorpromazine analogues exert antiproliferative effects by inducing cell cycle arrest in the S phase and, consequently, apoptosis. [ABSTRACT FROM AUTHOR]

The starting compound 3-amino-1,7-dihydro-4H-pyrazolo[4,3-c]pyridine-4,6(5H)-dione (1) is reacted with each of diketone and β-ketoester, forming pyridopyrazolo[1,5-a]pyrimidines 4a,b and 14a,b, respectively. The compounds 4 and 14 reacted with each of aromatic aldehyde and arenediazonium salt to give the respective arylidenes and arylhydrazo derivatives, respectively. The structure of the new products was established using spectroscopic techniques. The cytotoxic activity of selected targets was tested in vitro against three cancer cell lines MCF7, HepG2 and HCT116. The data obtained from enzymatic assays of TrKA indicated that compounds 7b and 16c have the strongest inhibitory effects on TrKA with IC50 = 0.064 ± 0.0037 μg/ml and IC50 = 0.047 ± 0.0027 μg/ml, respectively, compared to the standard drug Larotrectinib with IC50 = 0.034 ± 0.0021 μg/ml for the HepG2 cancer cell line. In cell cycle analysis, compounds 7b, 15b, 16a and 16c caused the greatest arrest in cell cycle at the G2/M phase. In addition, compound 15b has a higher apoptosis-inducing effect (36.72%) than compounds 7b (34.70%), 16a (21.14) and 16c (26.54%). Compounds 7b, 16a and 16c were shown fit tightly into the active site of the TrKA kinase crystal structure (PDB: 5H3Q). Also, ADME study was performed on some selected potent anticancer compounds described in this study. Highlights: A series of new pyrido[4ʹ,3ʹ:3,4]pyrazolo[1,5-a]pyrimidine derivatives were synthesized. The anticancer activity of the new compounds were tested in vitro. Compounds 7b and 16c showed broad spectrum potent anticancer activity. Compound 15b induced cell cycle arrest at G2/M phase in HepG-2 cell line. Compound 7c, the most promising agent, can be absorbed very easily by the gastrointestinal tract with potential BBB permeability. [ABSTRACT FROM AUTHOR]

Oxypeucedanin (OPD) as a powerful anti-proliferative agent found in the Angelicae dahuricae has been used to suppress cancer cell growth. However, the hydrophobic chemical structure has limited its solubility and bio-accessibility. This is the first time OPD is encapsulated into a nano-liposomal structure and coated with poly-cationic chitosan polymer as the oxypeucedanin drug delivery system to evaluate its antioxidant and anti-colon cancer potential. The chitosan-coated oxypeucedanin nano-chitosomes (COPD-NCs) were synthesized utilizing the thin-layer hydration method and characterized by FESEM, DLS, FTIR, and zeta potential analysis. The anti-cancer potential of COPD-NC was analyzed by measuring the cell survival rate (MTT assay) and studying the cellular death type (AO/PI staining) following the increased treatment concentrations of COPD-NC on the HT-29 colon cancer cell line. Moreover, the COPD-NCs' apoptotic activity was verified by analyzing Cas-3 and Cas-9 gene expression profiles. Finally, the COPD-NCs' antioxidant activity was evaluated by applying ABTS, DPPH, and FRAP antioxidant assays. The 258.26-nm COPD-NCs significantly inhibited the HT-29 colon cancer cells compared with the normal fibroblast HFF cells. The up-regulated Cas-3 and Cas-9 gene expression exhibited the COPD-NCs' apoptotic activity. Also, the COPD-NCs' apoptotic activity was verified by detecting the increased apoptotic bodies following the AO/PI fluorescent staining in the increased exposure doses of COPD-NCs. Ultimately, the COPD-NCs meaningfully inhibited the ABTS-DPPH radicals and exhibited an appropriate FRAP-reductive potential. The designed nanostructure for COPD-NCs significantly improved its antioxidant potential and selective cytotoxicity on human HT-29 human cancer cells, which makes them a safe selective natural drug delivery system. Therefore, the COPD-NCs can selectively induce apoptotic death in human HT-29 cancer cells and have the potential to be studied as an anti-colon cancer compound. However, further cancer and normal cell lines are required to verify their selective cytotoxicity. [ABSTRACT FROM AUTHOR]

Objective(s): Harmaline and green-synthesized silver nanoparticles were encapsulated by folate-linked chitosan molecules as a receptor-mediated drug delivery system to evaluate its pro-apoptotic and anti-metastatic potentials on human ovarian (A2780) and epithelioid (PANC) cancer cells.Materials and Methods: The Ag nanoparticles (AgNP) were synthesized utilizing an herbal bio-platform (Bistorta officinalis) and embedded with harmalin. The Harmaline-ag containing folate-linked chitosan nanoparticles (HA-fCNP) were synthesized utilizing the ionic gelation method. Both the AgNP and HA-fCNP nanoparticles were characterized by DLS, FESEM, and Zeta potential analysis. Moreover, the chemical properties of HA-fCNP and the crystallinity of AgNPs were determined by applying FTIR and XRD methods, respectively. The HA-fCNP cytotoxicity was analyzed on A2780, PANC, and HFF cell lines. Moreover, pro-apoptotic and anti-metastatic potentials of HA-fCNP were studied by analyzing the BAX-BCL2 and MMP2-MMP9 gene expression profiles, respectively. The A2780 cellular death was determined by AO/PI and flow cytometry methods. Results: The HA-fCNP significantly exhibited a selective cytotoxic impact on A2780 and PANC cancerous cell lines compared with normal human foreskin fibroblast (HFF) cells. The increased SubG1-arrested A2780 cells and up-regulated BAX gene expression following the increased treatment concentrations of hA-fCNP indicated its selective pro-apoptotic activity on A2780 cells. Also, the notable down-regulated expressions of MMP2 and MMP9 metastatic genes following the increasing doses of HA-fCNP treatment on A2780 cells confirmed its anti-metastatic activity.Conclusion: The cancer-selective cytotoxicity, apoptotic, and anti-metastatic properties of HA-fCNP are considered the appropriate properties of an anticancer compound.

Objective(s): Harmaline and green-synthesized silver nanoparticles were encapsulated by folatelinked chitosan molecules as a receptor-mediated drug delivery system to evaluate its pro-apoptotic and anti-metastatic potentials on human ovarian (A2780) and epithelioid (PANC) cancer cells. Materials and Methods: The Ag nanoparticles (AgNP) were synthesized utilizing an herbal bioplatform (Bistorta officinalis) and embedded with harmalin. The Harmaline-ag containing folatelinked chitosan nanoparticles (HA-fCNP) were synthesized utilizing the ionic gelation method. Both the AgNP and HA-fCNP nanoparticles were characterized by DLS, FESEM, and Zeta potential analysis. Moreover, the chemical properties of HA-fCNP and the crystallinity of AgNPs were determined by applying FTIR and XRD methods, respectively. The HA-fCNP cytotoxicity was analyzed on A2780, PANC, and HFF cell lines. Moreover, pro-apoptotic and anti-metastatic potentials of HA-fCNP were studied by analyzing the BAX-BCL2 and MMP2-MMP9 gene expression profiles, respectively. The A2780 cellular death was determined by AO/PI and flow cytometry methods. Results: The HA-fCNP significantly exhibited a selective cytotoxic impact on A2780 and PANC cancerous cell lines compared with normal human foreskin fibroblast (HFF) cells. The increased SubG1-arrested A2780 cells and up-regulated BAX gene expression following the increased treatment concentrations of hA-fCNP indicated its selective pro-apoptotic activity on A2780 cells. Also, the notable down-regulated expressions of MMP2 and MMP9 metastatic genes following the increasing doses of HA-fCNP treatment on A2780 cells confirmed its anti-metastatic activity. Conclusion: The cancer-selective cytotoxicity, apoptotic, and anti-metastatic properties of HA-fCNP are considered the appropriate properties of an anticancer compound. [ABSTRACT FROM AUTHOR]

Cancer is a broad classification of diseases that can affect any organ or body tissue due to aberrant cellular proliferation for unknown reasons. Many present chemotherapeutic drugs are highly toxic and have little selectivity. Additionally, they lead to the development of medication resistance. Therefore, developing tailored chemotherapeutic drugs with minimal side effects and good selectivity is crucial for cancer treatment. 2-(1H)-Quinazolinone is one of the vital scaffold and anticancer activity is one of the prominent biological activities of this class. Here we report the novel set of amide-enriched 2-(1H)-quinazolinone derivatives (7a-j) and their apoptotic activity with the help of MTT assay method against four human cancer cell lines: PC3 (prostate cancer), DU-145 (prostate cancer), A549 (lung cancer), and MCF7 (breast cancer). When compared to etoposide, every synthetic test compound (7a-j) exhibited moderate to excellent activity. The IC50 values of the new amide derivatives (7a-j) varied from 0.07 ± 0.0061 μM to 10.8 ± 0.69 μM. While the positive control, etoposide, exhibited 1.97 ± 0.45 μM to 3.08 ± 0.135 μM range. Among the novel amide derivatives (7a-j), in particular, 7i and 7j showed strong apoptotic activity against MCF7; 7h showed against PC3, and 7g showed against DU-145. Molecular docking studies of test compounds (7a-j) with the EGFR tyrosine kinase domain (PDB ID: 1M17) protein provided the significant docking scores for each test compound (7a-j) (−9.00 to −9.67 kcal/mol). Additionally, DFT investigations and MD simulations validated the predictions of molecular docking. According to the findings of the ADME analysis, oral absorption by humans is anticipated to be higher than 85 % for all test compounds.

Clove plant (Syzygium aromaticum) is one of the Myrtaceae family. It's a common flavor in food and the traditional medicine. The study's objective was to ascertain whether the clove bud aqueous extract (CAE) and CAE + nanosilver have any biological effects on immune cells and HT-29 colon cancer cell line. Nanosilver was produced through green synthesis approach using CAE. Produced nanosilver was characterized via electron microscope (scanning, SEM) and ultraviolet-visible spectroscopy. CAE and CAE + nanosilver were examined for their active biomolecules using FTIR analysis, p53 contents using real-time PCR, apoptosis and cell cycle arrest power on HT-29 cancer cell line via flow cytometerty and immunomodulatory potential utilizing MTT assay. Results cleared that a spherical nanosilver with a diameter range of 53 nm was formed by CAE. There were several active biomolecules in CAE and CAE + nanosilver. CAE and CAE + nanosilver increased the p53 protein expression and apoptotic cell number in HT-29 colon cancer cells. CAE and CAE + nanosilver could arrest HT-29 cells at the phase G2/M. CAE and CAE + nanosilver stimulated quiescent and PHA-pre-treated splenic cells at higher concentrations, and CAE suppressed quiescent splenic cell when diluted. In conclusion, the safe edible Syzygium aromaticum plant can be utilized to make anti-tumor agent, essentially for colon tumor. As Syzygium aromaticum plant could stimulate immune cells, it can be used as immune-stimulatory agent that can help fight tumor and tumor development. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the differences in the chemical composition of the essential oils and hydrosols of six different Veronica species (V. agrestis, V. anagalloides, V. austriaca ssp. jacquinii, V. beccabunga, Veronica cymbalaria, and V. officinalis) and to test their antiproliferative and apoptotic activities, according to the authors' knowledge, because of insufficient research and lack of information. Also, the goal was to determine which obtained samples were better in achieving antiproliferative and apoptotic activities and due to which volatile components. Therefore, essential oils (EOs) and hydrosols (HYs) were isolated from the above-mentioned Veronica species by microwave-assisted extraction (MAE). Phytochemical identification of the free volatile compounds was performed using a GC equipped with a flame ionization detector and a mass spectrometer. Their antiproliferative and apoptotic activities against two human cancer cell lines, breast cancer cell line MDA-MB-231 and bladder cancer cell line T24, were determined. The main compounds identified in the studied Veronica EOs and HYs were terpinen-4-ol (0.34–6.49%), linalool (0.34–6.61%), (E)-caryophyllene (0.97–7.55%), allo-aromadendrene (0.18–2.21%), caryophyllene oxide (1.42–23.83%), benzene acetaldehyde (0.26–13.34%), and β-ionone (1.08–16.53%). In general, HYs of the tested Veronica species showed higher antiproliferative activity (IC50 13.41–42.05%) compared to EOs (IC50 158.1–970.4 µg/mL) on MDA-MB-231 and T24 cancer cell lines after 48 and 72 h. V. agrestis EO showed the best apoptotic effect among the EOs on the MDA-MB-231 cancer cell line (10.47 ± 0.53% and 9.06 ± 0.74% of early/late apoptosis, compared with control 3.61 ± 0.62% and 0.80 ± 0.17% of early/late apoptosis, respectively) and among the HYs V. cymbalaria showed 9.95 ± 1.05% and 3.06 ± 0.28% of early/late apoptosis and V. anagalloides 8.29 ± 1.09% and 1.95 ± 0.36% of early/late apoptosis compared with control (for EO was 7.45 ± 1.01% and 0.54 ± 0.25%, and for HY was 4.91 ± 1.97% and 0.70 ± 0.09% of early/late apoptosis, respectively) on the T24 cancer cell line. Future research will include other Croatian species of the genus Veronica to gain a more complete insight into the biological activity of the volatile products of this genus for potential discovery of drugs based on natural plant extracts. [ABSTRACT FROM AUTHOR]

Abstract Background Various types of cancer therapy strategies have been investigated and successfully applied so far. There are a few modern strategies for improving drug selectivity and biocompatibility, such as nanoparticle-based drug delivery systems. Herein, we designed the traceable enzyme-conjugated magnetic nanoparticles to target human breast cancer cells by simulating the innate immune cell’s respiratory explosion response. Methods The human immune cell simulated anti-breast cancer-nanorobot (hisABC-NB) was produced by conjugating the mouse-derived iNOS and human-originated MPO enzymes on the folate-linked chitosan-coated Fe3O4 nanoparticles. The synthesized nanoparticles were functionalized with folic acid as the breast cancer cell detector. Then, the hisABC-NB’s stability and structural properties were characterized by studying Zeta-potential, XRD, FTIR, VSM, FESEM, and DLS analysis. Next, the selectivity and anti-tumor activity of the hisABC-NB were comparatively analyzed on both normal (MCF-10) and cancerous (MCF-7) human breast cells by analyzing the cells’ survival, apoptotic gene expression profile (P53, BAX, BCL2), and flow cytometry data. Finally, the hisABC-NB’s traceability was detected by T2-weighted MRI imaging on the balb-c breast tumor models. Results The hisABC-NB significantly reduced the MCF-7 human breast cancer cells by inducing apoptosis response and arresting the cell cycle at the G2/M phase compared with the normal cell type (MCF-10). Moreover, the hisABC-NB exhibited a proper MRI contrast at the tumor region of treated mice compared with the non-treated type, which approved their appropriate MRI-mediated traceability. Conclusion The hisABC-NB’s traceability, dirigibility, and selective cytotoxicity were approved, which are the three main required factors for an efficient anticancer compound. Therefore, it has the potential to be used as an intelligent safe anticancer agent for human breast cancer treatment. However, several in vitro and in vivo studies are required to clarify its selectivity, stability, and safety.

Background: Various types of cancer therapy strategies have been investigated and successfully applied so far. There are a few modern strategies for improving drug selectivity and biocompatibility, such as nanoparticle-based drug delivery systems. Herein, we designed the traceable enzyme-conjugated magnetic nanoparticles to target human breast cancer cells by simulating the innate immune cell's respiratory explosion response. Methods: The human immune cell simulated anti-breast cancer-nanorobot (hisABC-NB) was produced by conjugating the mouse-derived iNOS and human-originated MPO enzymes on the folate-linked chitosan-coated Fe3O4 nanoparticles. The synthesized nanoparticles were functionalized with folic acid as the breast cancer cell detector. Then, the hisABC-NB's stability and structural properties were characterized by studying Zeta-potential, XRD, FTIR, VSM, FESEM, and DLS analysis. Next, the selectivity and anti-tumor activity of the hisABC-NB were comparatively analyzed on both normal (MCF-10) and cancerous (MCF-7) human breast cells by analyzing the cells' survival, apoptotic gene expression profile (P53, BAX, BCL2), and flow cytometry data. Finally, the hisABC-NB's traceability was detected by T2-weighted MRI imaging on the balb-c breast tumor models. Results: The hisABC-NB significantly reduced the MCF-7 human breast cancer cells by inducing apoptosis response and arresting the cell cycle at the G2/M phase compared with the normal cell type (MCF-10). Moreover, the hisABC-NB exhibited a proper MRI contrast at the tumor region of treated mice compared with the non-treated type, which approved their appropriate MRI-mediated traceability. Conclusion: The hisABC-NB's traceability, dirigibility, and selective cytotoxicity were approved, which are the three main required factors for an efficient anticancer compound. Therefore, it has the potential to be used as an intelligent safe anticancer agent for human breast cancer treatment. However, several in vitro and in vivo studies are required to clarify its selectivity, stability, and safety. [ABSTRACT FROM AUTHOR]

Introduction: Gratiola officinalis L. (hedge hyssop), a medicinal plant of the Scrophulariaceae family, has diuretic, purgative, and vermifuge properties. It is used as a herbal tea to treat chronic gastroenteritis, renal colic, jaundice, and intestinal worms. Previously, we have found that an extract from G. officinalis is nontoxic and has antitumor, antioxidant, antimicrobial, antiinflammatory, anticachexic, and other properties. Our aims in this study were to separate the G. officinalis extract into individual fractions, to identify the most biologically active fractions, and to examine the chemical composition of these fractions and their biological activity toward A498 renal carcinoma cells., Methods: The G. officinalis extract was fractionated by reversed-phase high-performance liquid chromatography, and each fraction was tested for antitumor activity. The active fractions were characterized by UV-visible electron spectral analysis, circular dichroism analysis, Fourier transform infrared spectroscopy, high-performance liquid chromatography, electrospray ionization tandem mass spectrometry, and nuclear magnetic resonance spectroscopy., Results: Two antitumor-active fractions of a flavonoid nature were isolated and chromatographically purified. On the basis of the nuclear magnetic resonance data, the aglycone fragment of the main component of one fraction was found to be structured as 2-(3,4-dimethoxyphenyl)-7-hydroxychroman-4-one, or 3',4'-dimethoxy-7- hydroxyflavanone., Conclusion: The antitumor effect of the most active fraction containing 7-O-glucoside of apigenin, glycoside 7,3'-di-O-luteolin and trace amounts of eupatilin against renal carcinoma A498 cells was manifested in its cytotoxic, cytostatic, apoptotic and autophagosomal activities. In addition, we found 3-(1-2)-glucoside of soyaspogenol B, which is a pentacyclic triterpenoid in the structure., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A unique case of multiple metastatic melanoma skin nodules regression in a heavily pretreated, 72-year-old Caucasian female, after administering the second dose of the SARS-CoV-2 mRNA Pfizer-BioNTech vaccine, is presented. Two days after vaccination, all her melanoma skin nodules became painful and were significantly reduced in size. Physical examination and ultrasound imaging confirmed the patient's observation. The effect was sustained, and further reduction of the nodules occurred after the third vaccine dose. One of the reduced nodules was removed, histologically examined, and its histopathology was compared to that of another such nodule removed and examined earlier. Distinct differences were observed between the two histopathologies, with the most notable the unexpected finding of the absence of infiltrating lymphocytes in the reducer nodule's melanoma tissue. Based on this observation, the possible immunological mechanism(s) leading to the vaccine's effect are speculated. More possible is the vaccine's antitumor and apoptotic activity via stimulation of the Tol Like Receptors 3, 7, and 8, and (downstream) the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway of the non-lymphocytic immune effector cells. [ABSTRACT FROM AUTHOR]

Newly synthesised benzimidazole/benzotiazole derivatives bearing amidino, namely 3,4,5,6-tetrahydropyrimidin-1-ium chloride, substituents have been evaluated for their potential antitumor activity in vitro. Compounds and standard drugs (doxorubicin, staurosporine and vandetanib) were tested on three human lung cancer cell lines A549, HCC827 and NCI-H358. We tested compounds in MTS citotoxicity assay and in BrdU proliferative assay performed on 2 D and 3 D assay format. Because benzmidazole scaffold is similar to natural purines, we tested the most active compounds for ability to induce cell apoptosis of A549 by binding to DNA in comparison with doxorubicin and saturosporine. Additionally, the ADME properties of the most active benzothiazole/benzimidazole and non-active compounds were determined to see if the different ADME properties are the cause of different activity in 2 D and 3 D assays, as well as to see if the tested active compounds have drug like properties and potency for further profilation. ADME characterisation included solubility, lipophilicity, permeability, metabolic stability and binding to plasma proteins. In general, the benzothiazole derivatives were more active in comparison to their benzimidazole analogues. The exception was 2-phenyl substituted benzimidazole 6a being active with very pronounced activity especially towards HCC827 cells. All active compounds have similar mode of action on A549 cell line as standard compound doxorubicin, which binds to nucleic acids with the DNA double helix. Tested active benzothiazole compounds were characterised by moderate to good solubility, good metabolic stability, low permeability and high binding to plasma proteins. One tested active benzimidazole derivative showed ADME properties, but lower lipophilicity resulted in low PPB and higher metabolic instability. In addition, no significant difference was observed in ADME profile between active and non-active compounds.

Artemisia vulgaris essential oil (AVEO) is known as a therapeutic agent. Several types of investigation have demonstrated its cytotoxic impact on human cancer cells. In the current study, AVEO nanoemulsion (AVEO-NE) was synthesized using an ultrasound-based emulsification method and its cytotoxic, apoptotic, antioxidant, and anti-angiogenic properties were evaluated for the MCF-7 cancer cell line by measuring the cell's gene expression profile and performing MTT. Finally, the anti-angiogenic activity of AVEO-NE was verified by applying CAM assay analysis. The results showed that AVEO-NE exhibited significant cell-selective cytotoxic, apoptotic, and antioxidant activities by up-regulating Cas-9, CAT, and SOD gene expression. Moreover, the AVEO-NE meaningfully suppressed angiogenesis in MCF-7 cancer cells by down-regulating VEGF gene expression. Finally, the decreased number and length of chick embryo chorioallantoic membrane (CAM) blood vessels verified AVEO-NE's anti-angiogenic activity. Therefore, AVEO-NE can potentially be employed as a safe cell-dependent anti-breast cancer drug delivery system. [ABSTRACT FROM AUTHOR]

This study was done to improve the medicinal properties of Syzygium Aromaticum L by processing S. Aromaticum L. bud essential oil (SABE) to the Nanoemulsion drug delivery system (SABE-NE) and investigating its anti-tumor and apoptotic impacts against the human HT-29 colon cancer cells. Applying the ultra-sonication method and characterization by DLS and FESEM analysis facilitates the nanoemulsification procedure. Human cancer (HT-29) and normal (HFF) cell lines were then evaluated based on the SABE-NE apoptotic and cytotoxic effects. In an in vitro section, flow cytometry method, Cas3 gene profile, AO/PI cell staining, and MTT assays are used to analyze the apoptotic and cytotoxic activities. In further analysis, liver lipid peroxidation and antioxidant genes expression (SOD, CAT, and GPx) investigate alterations in mice organs. As a result, produced 131.2 nm SABE-NE induces apoptosis response and cellular death (Cas3 up-regulation and enhanced SubG1 peaks). Subsequently, the HT-29 cells' viability can reduce significantly, while HFF cells indicate confined cytotoxic impacts. Moreover, in vivo test results on mice livers demonstrate the cytoprotective properties of SABE-NE (reduced lipid peroxidation and increased antioxidant enzymes gene expression and nondetectable cytotoxic impacts). We produced a novel nanoemulsion drug delivery system called SABE-NE, a cell-specific apoptotic inducer. We thus can be utilized as an efficient anti-cancer compound for human colon cancer treatment. However, further supplementary studies are required to verify and approve its cell-specific anti-tumor activity. [ABSTRACT FROM AUTHOR]

Newly synthesised benzimidazole/benzotiazole derivatives bearing amidino, namely 3,4,5,6-tetrahydropyrimidin-1-ium chloride, substituents have been evaluated for their potential antitumor activity in vitro. Compounds and standard drugs (doxorubicin, staurosporine and vandetanib) were tested on three human lung cancer cell lines A549, HCC827 and NCI-H358. We tested compounds in MTS citotoxicity assay and in BrdU proliferative assay performed on 2 D and 3 D assay format. Because benzmidazole scaffold is similar to natural purines, we tested the most active compounds for ability to induce cell apoptosis of A549 by binding to DNA in comparison with doxorubicin and saturosporine. Additionally, the ADME properties of the most active benzothiazole/benzimidazole and non-active compounds were determined to see if the different ADME properties are the cause of different activity in 2 D and 3 D assays, as well as to see if the tested active compounds have drug like properties and potency for further profilation. ADME characterisation included solubility, lipophilicity, permeability, metabolic stability and binding to plasma proteins. In general, the benzothiazole derivatives were more active in comparison to their benzimidazole analogues. The exception was 2-phenyl substituted benzimidazole 6a being active with very pronounced activity especially towards HCC827 cells. All active compounds have similar mode of action on A549 cell line as standard compound doxorubicin, which binds to nucleic acids with the DNA double helix. Tested active benzothiazole compounds were characterised by moderate to good solubility, good metabolic stability, low permeability and high binding to plasma proteins. One tested active benzimidazole derivative showed ADME properties, but lower lipophilicity resulted in low PPB and higher metabolic instability. In addition, no significant difference was observed in ADME profile between active and non-active compounds. [ABSTRACT FROM AUTHOR]

2-Cyanopyrazolo[1,5-a]pyrimidine derivative 3 reacted with some aromatic aldehydes, arenediazonium salts, hydrazine hydrate, and guanidine hydrochloride to create a series of novel pyrazolo[1,5-a]pyrimidine derivatives. Spectroscopic data confirmed the structure of the newly synthesized compounds. Some target compounds were tested in vitro for anticancer efficacy against three cancer cell lines: HepG-2, MCF-7, and Hela. On the most efficient anticancer compounds 6b,c, 6f, and 6h,i, the CDK-2 enzyme was evaluated. Using the HepG-2 cancer cell line, compounds 6b and 6i demonstrated the most effective inhibitory activity against CDK-2, with IC50 values of 0.199 ± 0.005 μg/ml and IC50 = 0.206 ± 0.007 μg/ml, respectively, compared to Dinaciclib and Roscovitine, which had IC50 values of 0.021 ± 0.002 and 0.230 ± 0.007 μg/ml, respectively. In cell cycle assay, compounds 6b, 6f and 6i arrest cell cycle at G2/M, G1/S and G2/M phases, respectively. Compound 6f has a stronger apoptosis induction effect (27.82%) than compounds 6b (7.92%) and 6i (19.21%). Also, silico studies (Molecular docking and Lipinski's rules) for compounds 6b, 6f and 6i were carried out. [ABSTRACT FROM AUTHOR]

Preconditioning exercise prior to stroke exerts neuroprotection, which is an endogenous strategy that leads the brain cells to express several intrinsic factors and inhibits their apoptosis. However, it is unclear how long these benefits last after exercise cessation. The aim of this study was to investigate the effects of detraining on preconditioning exercise-induced neuroprotective potential after stroke. Rats were trained using a treadmill for aerobic exercise 5 days each week for 3 weeks, and their neuroprotective effects were examined until 3 weeks after exercise cessation. Stroke was induced by 60 min of left middle cerebral artery occlusion at 3 days, 1, 2, and 3 weeks after exercise cessation. Infarct volume, neurological deficits, sensorimotor function, expression levels of brain-derived neurotrophic factor (BDNF), hypoxia-induced factor-1α (HIF-1α), glial fibrillary acidic protein (GFAP), and P2X7 receptors, and apoptosis activity were examined using immunohistochemical and western blot analyses. Preconditioning exercise significantly reduced infarct volume and ameliorated sensorimotor function after stroke, and its beneficial effects were observed until 2 weeks after exercise cessation. The expression level of BDNF in the ischemic brain was significantly upregulated at 3 days after exercise cessation; however, the expression levels of HIF-1α, GFAP, and P2X7 receptor were significantly increased until 2 weeks after exercise cessation; thereby, significant anti-apoptotic effects were lost at 3 weeks of detraining. Our findings suggest that preconditioning exercise-induced neuroprotective potential may be lost shortly after exercise cessation. Neuroprotection through intrinsic protective factors, such as BDNF and HIF-1α, may provide different neuroprotective mechanisms in a time-dependent manner during detraining. [ABSTRACT FROM AUTHOR]

Nano-biotechnology has grown rapidly and become an integral part of modern disease diagnosis and treatment. The aim of this survey was to evaluate the anticancer activity of synthesized selenium nanoparticles (Se-NPs) against breast cancer cells (MCF-7). The prepared Se-NPs were examined by ultraviolet-visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscope (SEM), and energy dispersive spectroscopy (EDX). Antioxidant activity of Se-NPs property was studied by radical scavenging (DPPH) assay. The in-vitro cytotoxicity of Se-NPs was evaluated by MTT assay. In addition; the biological assessment (antioxidant and cytotoxicity) of synthesized Se-NPs was examined via molecular docking simulations. Synthesis of Se-NPs was characterized by several studies such as UV-absorbance, showing peak values in the range of 268 nm. Nanoparticle sizes of the nanoparticles are confirmed by dynamic light scattering analysis, indicating that average size is about 203 nm. The quantity of selenium in Se-NPs is 90.15% by weight, as confirmed by EDX. Synthesized Se-NPs have anti-proliferative effects on MCF-7 cell lines. Cytotoxicity and apoptotic potential assays exhibited a dose-dependent effect against MCF-7 cells using an MTT assay. Like anti-cancer activity, anti-oxidant activity of Se-NPs was dose-dependent. Findings showed that the Se-NPs complexes have the highest inhibitory effect against cytotoxic and antioxidant receptors. Results of this study demonstrated that Se-NPs had strong potential to scavenge free radicals and are cytotoxic against the MCF-7 cancer cell line. [ABSTRACT FROM AUTHOR]

Abstract Background The present study involves diversity and bioactivity of the endophytic fungal community from Catharanthus roseus inhabiting the coastal region. This study has been conducted hypothesizing that the microbial communities in the coastal regions would tolerate a range of abiotic stress such as salinity, humidity, temperature and soil composition, and it may produce new metabolites, which may possess bioactive property. Therefore in the current study, the cytotoxicity and free radical scavenging potential of the fungal organic extracts have been investigated. Moreover, the apoptotic and the antioxidant potential of the fungus that exhibited the best activity in preliminary screening has also been demonstrated. Results Twenty endophytic fungal isolates were obtained from different parts of the plant, and identified using internal transcribed spacer region analysis. Based on the colonization frequency, the dominant genera were found to be Colletotrichum, Alternaria and Chaetomium with colonization frequency % of 8.66, 7.00 and 6.33, respectively. It was observed that the species diversity and richness was the highest in bark followed by leaf and stem regions of the plant. On screening the fungal ethyl acetate extracts for cytotoxicity against the HeLa cells, the Chaetomium nigricolor extract exhibited potent cytotoxic activity of 92.20% at 100 μg mL− 1 concentration. Comparison between the different organic extracts (ethyl acetate, chloroform, dichloromethane and hexane) of Chaetomium nigricolor mycelial and culture filtrate, it was observed that the mycelial as well the culture filtrate ethyl acetate extracts and the culture filtrate hexane extract showed significant cytotoxic potential against the HeLa and MCF-7 cells, respectively. The apoptotic- and mitochondrial membrane depolarisation-induction potential of the Chaetomium nigricolor ethyl acetate extract has also been demonstrated in this study. Further the screening of antioxidant potential of the ethyl acetate fungal extracts using DPPH scavenging assay showed that Chaetomium nigricolor extract exhibited potential activity with a significant EC50 value of 22 μg mL− 1. The ethyl acetate extract of Chaetomium nigricolor also exhibited superoxide radical scavenging potential. Conclusion These results indicated that diverse endophytic fungal population inhabits Catharanthus roseus. One of the fungal isolate Chaetomium nigricolor exhibited significant cytotoxic, apoptotic and antioxidant potential.

Cancer is a broad classification of diseases that can affect any organ or body tissue due to aberrant cellular proliferation for unknown reasons. Many present chemotherapeutic drugs are highly toxic and have little selectivity. Additionally, they lead to the development of medication resistance. Therefore, developing tailored chemotherapeutic drugs with minimal side effects and good selectivity is crucial for cancer treatment. 2-(1 H )-Quinazolinone is one of the vital scaffold and anticancer activity is one of the prominent biological activities of this class. Here we report the novel set of amide-enriched 2-(1 H )-quinazolinone derivatives ( 7a-j ) and their apoptotic activity with the help of MTT assay method against four human cancer cell lines: PC3 (prostate cancer), DU-145 (prostate cancer), A549 (lung cancer), and MCF7 (breast cancer). When compared to etoposide, every synthetic test compound ( 7a-j ) exhibited moderate to excellent activity. The IC 50 values of the new amide derivatives ( 7a-j ) varied from 0.07 ± 0.0061 μM to 10.8 ± 0.69 μM. While the positive control, etoposide, exhibited 1.97 ± 0.45 μM to 3.08 ± 0.135 μM range. Among the novel amide derivatives ( 7a-j ), in particular, 7i and 7j showed strong apoptotic activity against MCF7; 7h showed against PC3, and 7g showed against DU-145. Molecular docking studies of test compounds ( 7a-j ) with the EGFR tyrosine kinase domain (PDB ID: 1M17) protein provided the significant docking scores for each test compound ( 7a-j ) (-9.00 to -9.67 kcal/mol). Additionally, DFT investigations and MD simulations validated the predictions of molecular docking. According to the findings of the ADME analysis, oral absorption by humans is anticipated to be higher than 85 % for all test compounds., Competing Interests: 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., (© 2024 The Author(s).)

A unique case of multiple metastatic melanoma skin nodules regression in a heavily pretreated, 72-year-old Caucasian female, after administering the second dose of the SARS-CoV-2 mRNA Pfizer-BioNTech vaccine, is presented. Two days after vaccination, all her melanoma skin nodules became painful and were significantly reduced in size. Physical examination and ultrasound imaging confirmed the patient’s observation. The effect was sustained, and further reduction of the nodules occurred after the third vaccine dose. One of the reduced nodules was removed, histologically examined, and its histopathology was compared to that of another such nodule removed and examined earlier. Distinct differences were observed between the two histopathologies, with the most notable the unexpected finding of the absence of infiltrating lymphocytes in the reducer nodule’s melanoma tissue. Based on this observation, the possible immunological mechanism(s) leading to the vaccine’s effect are speculated. More possible is the vaccine’s antitumor and apoptotic activity via stimulation of the Tol Like Receptors 3, 7, and 8, and (downstream) the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway of the non-lymphocytic immune effector cells.

Synthesis of nanoparticles (NPs) from common food waste is an eco-friendly and cost-effective method. The present communication reports one-pot biosynthesis of silver nanoparticles (AgNPs) from Citrus sinensis (orange) peel extract (OPE). A clear synthesis of monodispersed AgNPs with average size of 22 nm has been indicated by UV–Vis spectrophotometry, dynamic light scattering and transmission electron microscopy and X-ray diffraction techniques. On the other hand, FTIR study clearly revealed that 'ether' and 'alcoholic' groups are mainly responsible for the stabilization of AgNPs. Theoretical simulation using density functional theory showed that among the alcoholic and ether groups, hotrienol is primarily responsible for the stabilization of AgNPs with the highest interaction energy of 62.92 kJ/mol. Synthesized AgNPs were found to induce apoptosis in model system hepatocellular carcinoma cell, Hep3B and showed increased percentages of late apoptotic cells. [ABSTRACT FROM AUTHOR]

Baccatin III is an important precursor for the synthesis of clinically important anticancer drug Taxol. Previously, we have characterized a key enzyme of 10-deacetylbaccatin III-10-β-O-acetyltransferase (DBAT) which catalyses the 10-deacetylbaccatin III into baccatin III in taxol biosynthesis. Here, in the present study, we have evaluated and compared the cytotoxic properties of the enzymatically synthesized baccatin III (ESB III) with standard baccatin III in different human cancer cell lines, namely human cervical cancer (HeLa), human lung cancer (A549), human skin cancer (A431) and human liver cancer cells (HepG2). Among the various cancer lines tested, HeLa was more susceptible to ESB III with IC50 of 4.30 µM while IC50 values for A549, A431 and HepG2 ranged from 4 to 7.81 µM. Further, it showed G2/M phase cell cycle arrest, production of reactive oxygen species and depolarised mitochondrial membrane potential. In addition, annexin V-FITC staining was performed which showed the apoptotic cell death of HeLa cells, when treated with ESB III. Hence, ESB III was capable to show anticancer activities by inducing apoptotic cell death which could further be used for the semisynthesis of taxol in future. [ABSTRACT FROM AUTHOR]

Cystic hydatid disease (CHD) is a zoonotic disease caused by the larval stage of Echinococcus granulosus (E. granulosus). This study aimed to synthesize silver nanoparticles (Ag NPs), silver boehmite nanocomposite (Ag/Bhm NC), and silver boehmite nanocomposite modified with chitosan (Ag/Bhm/Chit NC) using Rosmarinus officinalis (R. officinalis) extract and chemical method, and to evaluate their scolicidal and apoptotic effects on protoscoleces (PSCs) in vitro. The nanomaterials (NMs) were characterized by XRD, FTIR, FESEM, EDS, DLS, PDI, and zeta potential (ZP). The NMs were tested against PSCs at different concentrations (0.2-1.6 mg/mL) and exposure times (10-60 min). The size of Ag NPs, phytosynthesized Ag/Bhm NC, Ag/Bhm/Chit NC, and chemically synthesized Ag/Bhm NC were 25.55, 43, 72.3, and 60.8 nm, respectively. Ag NPs and phytosynthesized Ag/Bhm NC showed the highest scolicidal effect, with 65.34 % and 51.60 % mortality rate at 1.6 mg/mL and 60 min, respectively. Caspase-3 mRNA expression was higher in PSCs treated with Ag NPs and Ag/Bhm NC than in control groups (P < 0.05). Phytosynthesized Ag/Bhm NC had stronger scolicidal and apoptotic effect than chemically synthesized Ag/Bhm NC. Ag/Bhm/Chit NC had a weaker scolicidal effect but higher gene expression than Ag/Bhm NC. In conclusion, this study demonstrates the potential of phytosynthesized Ag NPs and Ag/Bhm NC as effective scolicidal and apoptotic agents against PSCs of hydatid cysts, which may be useful for the treatment of this disease., 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.)

Cystic hydatid disease (CHD) is a zoonotic disease with different clinical stages caused by the larval stage of the cestode Echinococcus granulosus. It is important to highlight as a public health problem in various regions of the world. In the current study, the efficacy and apoptotic activity of the liposomal system containing juglone (5-hydroxy-1,4-naphthoquinone) were assessed against protoscoleces (PSCs) in vitro. To this aim, firstly, liposomal vesicles were prepared by the thin-film method. Their physico-chemical features were assessed using Zeta-Sizer and Scanning Electron Microscope (SEM). Subsequently, various concentrations (50, 100, 200, 400, and 800 μg/mL) of juglone nanoliposomes at different exposure times (15, 30, 60, and 120 min) were used against PSCs. Results showed that juglone nanoliposomes at all tested concentrations induced scolicidal effect, however, 800 μg/mL and 400 μg/mL of juglone nanoliposomes could reach 100% mortality in 60 and 120 min, respectively. Additionally, we found that caspase-3 mRNA expression was higher in PSCs treated with juglone nanoliposomes compared to control groups (p < 0.001). Therefore, juglone nanoliposomes are suggested to have a more potent apoptotic effect on PSCs. Generally, optimized doses of juglone nanoliposomes could display significant scolicidal effects. Moreover, further in vivo studies are required to evaluate the efficacy of this nanoliposome.

The aim of the current study was to biosynthesize the silver nanoparticles (AgNPs) from the bacterial strain of Bacillus cereus (ATCC 14579) extracellularly. When bacterial extract was challenged with 1 mM silver nitrate (AgNO3) the color of the extract changed into brown confirms the formation of nanoparticles. These nanoparticles were capped with bovine serum albumin (BSA). UV- visible spectroscopy showed the absorption peak at 420 nm indicates the formation of AgNPs. Fourier Infra –red (FTIR) attenuated total reflection (ATR) spectroscopy showed amide and amine group associated with AgNPs that stabilizes the nanoparticles. Energy dispersive x-ray spectroscopy (EDX) showed a strong peak of silver confirms the presence of silver. Thermo gravimetric analysis (TGA) analysis was used to determine the protein degradation showed less protein degradation at higher temperature confirms the stability of nanoparticles. Transmission electron microscopy (TEM) showed the AgNPs are well dispersed and spherical, and 5.37 nm to 17.19 whereas albumin coated nanoparticles are size ranges from 11.26 nm to 23.85 nm. The anticancer effect of capped AgNPs (cAgNPs) showed the IC50 value against breast cancer MCF-7 at 80 μg/mL, intestinal colon cancer HCT- 116 60 μg/mL, and bone cancer osteosarcoma MG-63 cell line80 μg/mL while against normal fibroblast cells 3T3 cells showed the IC50 value at 140 μg/mL. Lactate dehydrogenase assay (LDH) showed higher toxicity on MCF-7, HCT-116, and MG-63 cells. The apoptotic study clearly showed the blebbing of membrane, chromatin condensation due to the production of reactive oxygen species (ROS) by ethidium bromide and acridine orange dual staining method. The DNA analysis showed the complete fragmentation of the DNA of treated cells when compared with control cells. Unlabelled Image • Bacillus cereus was used for the biosynthesis of silver nanoparticles (AgNPs). • AgNPs were capped with bovine serum albumin (cAgNPs). • cAgNPs showed high toxicity towards different cancer cells. • cAgNPs showed high release of lactate dehydrogenase. [ABSTRACT FROM AUTHOR]

• A series of forty α-substituted chalcones were synthesized. • Antiproliferative activity against HCT116 and HCC1954 cancer cell lines identified 5a and 5e as hits. • Both compounds induce a G2/M cell cycle arrest and cause apoptotic cell death. • Both compounds stabilized p53 in a dose-dependent manner in HCT116. • Both compounds were able to overcome multidrug resistance in two multidrug resistant cell lines. A series of forty α-substituted chalcones were synthesized and screened for their antiproliferative activities against HCT116 (colorectal) and HCC1954 (breast) cancer cell lines. Compounds 5a and 5e were found to be the most potent compounds with GI 50 values of 0.63 µM and 0.725 µM in HCC1954 cell line and 0.69 µM and 1.59 µM in HCT116 cell line, respectively. Both compounds induced a G2/M cell cycle arrest and caused apoptotic cell death in HCT116 cells as shown by the induction of PARP cleavage. The compounds also stabilized p53 in a dose-dependent manner in HCT116 cells following 24-hour treatment. Furthermore, both 5a and 5e were able to overcome multidrug resistance in two MDR-1 overexpressing multidrug resistant cell lines. [ABSTRACT FROM AUTHOR]

Abstract This study was designed to characterize the physico-chemical properties of the sulfated polysaccharide (SP) isolated from the red alga Laurencia obtusa and to evaluate its apoptotic, gastroprotective and antioxidant activities. The different macromolecular characteristics of SP were determined by size exclusion chromatography combined with multi-angle laser light-scattering detection (SEC-MALLS), Fourier transform infrared spectroscopy (FTIR) analysis and nuclear magnetic resonance spectroscopy (1H NMR and 13C NMR). The native molecular weight of the extracted polysaccharide is high (≥336,900 g·mol−1). It showed high amounts of sulfated groups (28.2%) and low levels of proteins. It was found to be a potent inducer of apoptosis on acute monocytic leukaemia THP-1cell lines with EC 50 value of 53 μg·mL−1. Furthermore, a significant gastroprotective effect (p < 0.01) was also observed with a gastric ulcer inhibition of 63.44%, 78.42% and 82.15% at the doses 25, 50 and 100 mg·kg−1, respectively. In addition, SP significantly increased glutathione levels (GSH) and decreased the concentration of thiobarbituric acid-reactive substances (TBARS) in EtOH/HCl-damaged gastric mucosa in rats; it also exhibited an important antioxidant activity in vitro. Therefore, SP, derived from the red alga Laurencia obtusa, may have a potential therapeutic effect against acute myeloid leukaemia and a beneficial potential as gastroprotective and antioxidant natural product. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Background: The present study involves diversity and bioactivity of the endophytic fungal community from Catharanthus roseus inhabiting the coastal region. This study has been conducted hypothesizing that the microbial communities in the coastal regions would tolerate a range of abiotic stress such as salinity, humidity, temperature and soil composition, and it may produce new metabolites, which may possess bioactive property. Therefore in the current study, the cytotoxicity and free radical scavenging potential of the fungal organic extracts have been investigated. Moreover, the apoptotic and the antioxidant potential of the fungus that exhibited the best activity in preliminary screening has also been demonstrated. Results: Twenty endophytic fungal isolates were obtained from different parts of the plant, and identified using internal transcribed spacer region analysis. Based on the colonization frequency, the dominant genera were found to be Colletotrichum, Alternaria and Chaetomium with colonization frequency % of 8.66, 7.00 and 6.33, respectively. It was observed that the species diversity and richness was the highest in bark followed by leaf and stem regions of the plant. On screening the fungal ethyl acetate extracts for cytotoxicity against the HeLa cells, the Chaetomium nigricolor extract exhibited potent cytotoxic activity of 92.20% at 100 μg mL− 1 concentration. Comparison between the different organic extracts (ethyl acetate, chloroform, dichloromethane and hexane) of Chaetomium nigricolor mycelial and culture filtrate, it was observed that the mycelial as well the culture filtrate ethyl acetate extracts and the culture filtrate hexane extract showed significant cytotoxic potential against the HeLa and MCF-7 cells, respectively. The apoptotic- and mitochondrial membrane depolarisation-induction potential of the Chaetomium nigricolor ethyl acetate extract has also been demonstrated in this study. Further the screening of antioxidant potential of the ethyl acetate fungal extracts using DPPH scavenging assay showed that Chaetomium nigricolor extract exhibited potential activity with a significant EC50 value of 22 μg mL− 1. The ethyl acetate extract of Chaetomium nigricolor also exhibited superoxide radical scavenging potential. Conclusion: These results indicated that diverse endophytic fungal population inhabits Catharanthus roseus. One of the fungal isolate Chaetomium nigricolor exhibited significant cytotoxic, apoptotic and antioxidant potential. [ABSTRACT FROM AUTHOR]

Aim. To study the effect of enalapril on functional activity and vitality of polymorphonuclear cells in rheumatic heart disease complicated by congestive heart failure.Material and methods. 81 patients with rheumatic heart disease and valvular disease were examined. There were 37 males (average age 53,6±9,7 y.o.) and 44 females (average age 56,2±9,6 y.o.). 25 healthy donors were involved as a control group. Neutrophils were isolated from the whole blood and cultivated during 6 h. Level of neutrophil nitric oxide production was assessed. Chemiluminescent assay was used to evaluate oxidative metabolism of neutrophils. Self-apoptotic activity of neutrophils was investigated by the determination of molecule bak on the surface of cellular membranes.Results. Redox metabolism and oxidative potential of granulocytes were increased in patients with rheumatic heart disease. Enalapril inhibited neutrophil functional and apoptotic activity and had favorable influence on the system of plasma antioxidant protection.Conclusion. The effect of enalapril can be associated with the increase of bradykinin and inhibition of angiotensin playing regulatory role in neutrophil function. Antiapoptotic effect of enalapril, probably, related to the modification of nitric oxide synthesis.

Background: Plants contain secondary metabolite used as drugs/medicines for the treatment of various diseases. Aristolochia tagala is used for the treatment of several diseases. Our study reported the chemopreventive potential of crude aqueous-methanol extract against diethylnitrosamine-induced hepatocellular carcinoma in BALB/c mice. A few articles have reported the presence of pharmacologically active compounds. Objective: Identification of biologically active compounds can give an insight into the mechanism of action of A. tagala and its potential development into modern drugs for the treatment of various diseases including cancer. Materials and Methods: Aqueous methanol extract (ATC) was prepared from roots of A. tagala and fractionated by column chromatography. The compounds present in ATC were identified and characterized by liquid chromatography (LC)–high-resolution mass spectrometry. ATC as well as the fractions (FI–FIV) were tested for their cytotoxic effect in HeLa cells by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and apoptotic events were analyzed by flow cytometry. The fraction that showed the most efficient cytotoxic effect against HeLa cells was purified by high-performance thin-layer chromatography. Purified compounds were again assayed for their apoptotic and cytotoxic effect. The most active compound was identified and characterized by electrospray ionization high-resolution mass spectrometry and LC–tandem-mass spectrometry. Statistical analysis was carried out using one-way anova followed by Tukey's multiple comparisons test. Results: A total of 21 compounds were identified; aristolochic acid I, aristolactam IIIa, β-sitosterol, kaempferol, and stigmasterol were previously reported in A. tagala and other compounds in other species of Aristolochia, and some compounds were reported to have anticancer, anti-inflammatory activities. From our study, compound S7 showed the highest cytotoxic and apoptotic activity and was identified as aristolochic acid I. Aristolochic acid earlier has been reported to have antitumor and anticancer effects, but lately, it has also been reported to have nephrotoxic effect. Conclusions: A. tagala was found to contain a number of compounds with reported biological activity. This plant and its related species can, therefore, be exploited for the extraction and isolation of these compounds with no toxicity. Abbreviations used: ATC: Aqueous-methanol extract, AA-I: Aristolochic acid I, CQA: Caffeoylquinic acid, CHCl3: Chloroform, MTT: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, ESI: Electrospray ionization, FITC: Fluorescein isothiocyanate, HCC: Hepatocellular carcinoma, HPLC: High-performance liquid chromatography, HRMS: High-resolution mass spectrometry, LC-MS/MS: LC-tandem-mass spectrometry, MeOH: Methanol, PBS: Phosphate buffered saline, PVDF: Polyvinylidene difluoride, RF: Radio frequency, R F: Retardation factor, XEVO-TQD: Xevo triple quadrupole [ABSTRACT FROM AUTHOR]

Background: Ziziphus obtusifolia is a spiny shrub found in Northwest Mexico desert, with traditional medicinal use to treat several diseases including cancer. Objective: The aims of the present study were to evaluate the antiproliferative and apoptotic activities of the aerial parts of this plant. Materials and Methods: The methanol extract and its fractions were prepared using several solvents. The antiproliferative activity was evaluated by the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium) (MTT) assay on HeLa, A549, RAW 264.7, M12.C3.F6 and L-929 cell lines, and the apoptotic activity using Annexin V and (5,50,6,60-tetra-chloro-1,10,3,30-tetra-ethylbenzimidazol-carbocyanine iodide) staining. The most active fraction was further separated by column chromatography. Results: The most active fraction was hexane with an IC50 of 90.4 μg/mL against RAW 264.7, 94 μg/mL against M12. C3.F6, 165.5 μg/mL against HeLa and 187.7 μg/mL against A549 cell lines. In apoptotic activity assays the methanol extract and its n-hexane fraction were found to induce mitochondrial depolarization in HeLa cells (83 and 87% respectively) and both induced the externalization of the phosphatidylserine increasing the percentage of cells in early apoptosis from 1.4% in untreated control cells, to 1.9% and 3.5% for methanol extract and n-hexane fraction-treated cells, respectively, statistically different for the total percentage of apoptotic cells (P < 0.05). Conclusions: These results show that Z. obtusifolia has antiproliferative and apoptotic activities in vitro and confirms its use in traditional medicine. [ABSTRACT FROM AUTHOR]

• Heterocyclic dithiocarbazate ligands were designed and synthesized. • The crystal structure of dithiocarbazate ligands was described. • BSA binding interactions with ligands through spectrofluorometric studies are discussed. • Anti-proliferative activity against the H520 cell lines was investigated. A series of organic based heterocyclic dithiocarbazate ligands N '-(1-methyl-1 H -imidazol-2-ylmethylene)-hydrazinecarbodithioic acid methyl ester (L1), N '-(1-methyl-1 H -imidazol-2-ylmethylene)-hydrazinecarbodithioic acid benzyl ester (L2), N '-[1-(1 H -benzoimidazol-2-yl)-ethylidene]-hydrazinecarbodithioic acid methyl ester (L3) and N '-[1-(1 H -benzoimidazol-2-yl)-ethylidene]-hydrazinecarbodithioic acid benzyl ester (L4) has been prepared along with characterization by various spectroscopic techniques (IR, 1H and 13C NMR, mass and UV–Visible) and thermal analysis. Single crystal X-ray diffraction analysis is used to determine the crystal structure of the synthesized ligands L1 and L3 crystallize s as orthorhombic and monoclinic crystals, respectively. Fluorescence spectrophotometry is used to study the interaction of the ligands with bovine serum albumin (BSA) and the quenching of BSA followed a static type. MTT assay against H520 (Squamous cell lung carcinoma) cell reveals that L1 and L3 ligands shows higher cytotoxic value than the remaining L2 and L4 ligands and could be a better choice as chemotherapeutic agent. Apoptotic activity was assayed using AO/EB staining and Hoechst 33258 staining, the early apoptotic features such as cell shrinkage and condensation were majorly observed in cells treated with all four ligands. [ABSTRACT FROM AUTHOR]

Antrodia cinnamomea (AC) has been widely used as a folk medicine in the prevention and treatment of liver diseases, such as hepatitis, hepatic fibrosis, and hepatocellular carcinoma. Previous studies have indicated that triterpenoids and benzenoids show selective cytotoxicity against human hepatoma cell lines. The aim of the study was to compare the triterpenoid content of extract and the extract-induced cytotoxicity in HepG2 cells from mycelia extracts of solid state cultured AC obtained by supercritical fluid extraction (SFE) and the conventional solvent extraction method. SFE with CO2 mixed with a constant amount of ethanol co-solvent (10% of CO2 volume) applied at different temperatures and pressures (40, 60 and 80 °C and, 20.7, 27.6 and 34.5 Mpa) was also compared in the study. Although the extraction yield of triterpenoids (59.7 mg/g) under the optimal extraction conditions of 34.5 MPa (5000 psi)/60 °C (designated as sample S-5000-60) was equivalent to the extraction yield using conventional liquid solvent extraction with ethanol (ETOH-E) at room temperature (60.33 mg/g), the cytotoxicity of the former against the proliferation of HepG2 cell line measured as the inhibition of 50% of cell growth activity (IC50) at dosages of 116.15, 57.82 and 43.96 µg/mL was superior to that of EtOH-E at 131.09, 80.04 and 48.30 µg/mL at 24, 48 and 72 h, respectively. Additionally, we further proved that the apoptotic effect of S-5000-60 presented a higher apoptosis ratio (21.5%) than ETOH-E (10.5%) according to annexin V-FITC and propidium iodide double staining assay results. The high affinity and selectivity of SFE on bioactive components resulted in a higher extraction efficiency than conventional solvent extraction. The chemical profile of the obtained extracts from solid state cultivated mycelium of AC was also determined by high-performance liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS), whereby three benzenoids and four triterpenoids were found for the first time in SFE extracts with 4,7-dimethoxy-5-methyl-l,3-benzodioxole (5.78 mg/g) being the most abundant component, followed by 2,4-dimethoxy-6-methylbenzene-1,3-diol (3.03 mg/g) and dehydroeburicoic acid (0.40 mg/g).

In this study, phthalonitriles 6, 7 and their corresponding bromo derivatives 8, 9 were synthesized from 8- hydroxyquinoline to investigate antiproliferative and cytotoxic activities on C6 (rat brain tumor), HeLa (human cervix carcinoma) and HT29 (human colon carcinoma) cancer cell lines of these molecules. The antiproliferative and apoptotic effects of 7-bromo- and 5,7-dibromo-8-hydroxyquinoline derivatives (2 and 3) and phthalonitrile 6, 7 and their brominated derivatives 8, 9 were compared in terms of Structure Activity Relationship (SAR). Although bromohydroxyquinoline derivatives 2 and 3 exhibited high antiproliferative activity according to literature, it has been determined that phthalonitrile compounds 6, 7 and their brominated 8, 9 derivatives are significantly reduced in antiproliferative activity. The SAR of the quinoline core at C-8 revealed that OH group lead to antiproliferative and apoptotic activity. In addition, biological activity was decreased when alkyl or substituted cyclic groups bounded to OH of quinoline, and the bromination of these derivatives did not increase the antiproliferative activity. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the safety and the short term apoptotic activity of intravitreal bevacizumab in rabbit eyes by histopathological analysis.METHODS:Twenty-eight eyes of 14 rabbits were divided into three groups:8 rabbits in group 1 and 3 rabbits in each of group 2 and group 3. Intravitreal bevacizumab (1.25mg/0.05mL) was applied to the right eyes of each subject in group 1 and group 2 (11 eyes) and the same volume of saline was applied to the left eyes of each subject in group 1 and group 3 (11 eyes). The left eyes in group 2 and the right eyes in group 3 were left untreated and used as control. Enucleated eyes were used for histopathologic analyses.RESULTS:After immunohistochemical staining with caspase-3 and p53, there was no histological evidence of toxicity to the retina and the optic nerve in any of the sections that were analyzed in all three groups. In addition, vascular endothelial cells located at the retina and the optic nerve tissues in all groups showed a similar staining pattern with caspase-3 and p53.CONCLUSION:Our study showed that intravitreal bevacizumab with the dose of 1.25mg/0.05mL caused no histological signs of toxicity or apoptotic activity on the rabbit retina.

Traditional or folk medicinal herbs continue to be prescribed in the treatment of various diseases and conditions in many cultures. Recent scientific efforts have focused on the potential roles of extracts of traditional herbs as alternative and complementary medications for cancer treatment. In Taiwan, Davallia divaricata Blume has been traditionally employed in folk medicine for therapy of lung cancer, davallic acid being the major active compound of D. divaricata Blume. In this study, we investigated the inhibitory activity of davallic acid on the proliferation of A549 lung cancer cells. Davallic acid was extracted from D. divaricata Blume, and its effects on cell viability, cell cycle distribution, ROS level, and apoptotic protein expression in A549 cells were determined. Davallic acid significantly induced reactive oxygen species (ROS) generation as well as caspase-3, -8, and -9 activation, thereby repressing A549 cell growth and elevating apoptotic activity. Since lung cancer has a high incidence of recurrence, these results indicate that davallic acid may have the potential to be a natural anti-lung cancer compound, and may provide a basis for further study of its use in combating cancer.

Summary Non-ionizing radiation at 2.45 GHz may modify the expression of genes that codify heat shock proteins (HSP) in the thyroid gland. Using the enzyme-linked immunosorbent assay (ELISA) technique, we studied levels of HSP-90 and HSP-70. We also used hematoxilin eosin to look for evidence of lesions in the gland and applied the DAPI technique of fluorescence to search for evidence of chromatin condensation and nuclear fragmentation in the thyroid cells of adult female Sprague-Dawley rats. Fifty-four rats were individually exposed for 30 min to 2.45 GHz radiation in a Gigahertz transverse electromagnetic (GTEM) cell at different levels of non-thermal specific absorption rate (SAR), which was calculated using the finite difference time domain (FDTD) technique. Ninety minutes after radiation, HSP-90 and HSP-70 had decreased significantly (P

Gastric cancer (GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. GC is the third greatest global cause of cancer-related deaths. It is well recognized that tumor heterogeneity, a fundamental feature of malignancy, plays an essential role in the cancer development and chemoresistance. In this study, we investigated the apoptotic effects of Pistacia vera nut skin methanol extract on human gastric cancer cell line HGC-27. The results of this study demonstrate for the first time the protective effect of Pistacia vera nut skin methanol extract on gastric carcinoma.

The differential availability of iron during hypoxia is presumed to affect the functioning of cardiac and skeletal myocytes. Rat H9C2 cardiomyocytes and L6G8C5 myocytes were cultured for 48 h in normoxic or hypoxic conditions at the optimal, reduced or increased iron concentration. The mRNA expression levels of markers of apoptosis [B-cell lymphoma-2 (Bcl2; inhibition) and Bcl-2-activated X protein (Bax; induction)], atrophy (Atrogin), glycolysis (pyruvate kinase 2; PKM2) and iron metabolism [transferrin receptor 1 (TfR1; iron importer), ferroportin 1 (FPN1; iron exporter), ferritin heavy chain (FTH; iron storage protein) and hepcidin (HAMP; iron regulator)] were determined using reverse transcription-quantitative polymerase chain reaction, and cell viability was measured using an tetrazolium reduction assay. Cardiomyocytes and myocytes, when exposed to hypoxia, demonstrated an increased Bax/Bcl-2 gene expression ratio (P<0.05). Additional deferoxamine (DFO) treatment resulted in further increases in Bax/Bcl-2 in each cell type (P<0.001 each) and this was associated with the 15% loss in viability. The analogous alterations were observed in both cell types upon ammonium ferric citrate (AFC) treatment during hypoxia; however, the increased Bax/Bcl-2 ratio and associated viability loss was lower compared with that in case of DFO treatment (P<0.05 each). Under hypoxic conditions, myocytes demonstrated an increased expression of PKM2 (P<0.01). Additional DFO treatment caused an increase in the mRNA expression levels of PKM2 and Atrogin-1 (P<0.001 and P<0.05, respectively), whereas AFC treatment caused an increased mRNA expression of PKM2 (P<0.01) and accompanied decreased mRNA expression of Atrogin-1 (P<0.05). The expression augmentation of PKM2 during hypoxia was greater upon low iron compared with that of ferric salt treatment (P<0.01). Both cell types upon DFO during hypoxia demonstrated the increased expression of TfR1 and HAMP (all P<0.05), which was associated with the increased Bax/Bcl-2 ratio (all R>0.6 and P<0.05). In conclusion, during hypoxia iron deficiency impairs the viability of cardiomyocytes and myocytes more severely compared with iron excess. In myocytes, during hypoxia iron may act in a protective manner, since the level of atrophy is decreased in the iron-salt-treated cells. [ABSTRACT FROM AUTHOR]

Objectives: This study was carried out to investigate apoptotic activity of Russula alboareolata ethanolic extract against L929, HepG2 and HeLa cells Methods: Fresh samples of R alboareolata from Kalasin, Mukdahan and Yasothon in the Northeastern part of Thailand. Dried samples were individually macerated with 95% ethanol with sonication for 1 hour to obtain crude extracts. Three cell lines including L929, HepG2 and HeLa purchased from ATCC were grown as adherent in DMEM at 37ºC in 5% CO2 incubator. Cells (1x105 cells/ml, 200 μl) were seeded onto 24 well plate and further grown for 24 hr. Apoptotic activity of R alboareolata extract was determined by mitochondrial membrane potential (MMP) assay using JC-1 fluorescent method. The L929, HeLa and HepG2 cells were treated for 24 hr with the extract at 600, 500 and 1,000 μg/ml,respectively. The chemotherapeutic drug, valinomycin was used as an apoptotic inducer and kept as a positive control. Apoptotic cells of L929, HeLa and HepG2 were analysed by fluorescent imaging system using the InCell 2200 Analyser (GE Healthcare, UK) following being stained with JC-1 and Hoechst 3342 reagents. Results: Valinomycin (1μg/ml) clearly induced apoptosis in L929, HeLa and HepG2 at 43.86, 36.85 and 40.00%, respectively. The percentages of apoptosis induced by R alboareolata extract was found as follows: L929 (77.20%, tested at 600 ug/ml), HeLa (73.69%, tested at 500 ug/ml), and HepG2 (30.00%, tested at 1,000 ug/ml), Conclusion: The ethanolic extract R. alboareolata possesses apoptotic activity against both normal (L929) and cancerous cells (HeLa and HepG2). However, we were unable to compare the degree of its apoptotic induction among these three cell lines due to the different concentrations used. Further studies including active constituents and in vivo experiments are required if this mushroom will be used as a novel dietary supplement and/or botanical-drug for chemoprevention. [ABSTRACT FROM AUTHOR]

Following a recent trend on the application of different pincer scaffolds for the development of new metal-based antitumor agents, in this work, dipeptides and dipeptide surrogates based on picolinyl- and 4-chloropicolinylamides with S -donor amino acid residues (cysteine, homocysteine, or methionine) bearing glycinate, alaninate, or phosphonate moieties either at the C -terminus or in the S -donor side arm have been designed as nonclassical pincer ligands with central amide units and shown to smoothly undergo site-selective direct cyclopalladation under mild conditions, affording the target Pd(II) pincer complexes in good to high yields. The realization of S,N,N -coordination through the sulfur atom of the thioether group and nitrogen atoms of the pyridine and deprotonated amide units was unambiguously confirmed using different NMR techniques (1H, 13C, 31P, and 2D NMR methods, including 1H 15N HMBC) and IR spectroscopy; the structure of one representative was elucidated by X-ray crystallography. The resulting pincer–(pseudo)dipeptide conjugates were screened for cytotoxicity against several cancer cell lines and noncancerous human embryonic kidney cells and at least some of them provided an appreciable level of activity comparable to that of cisplatin. The S -modified homocysteine-based derivatives exhibited also significant antiproliferative effects against doxorubicin-resistant transformed breast cells HBL100/Dox, implying the possibility of overcoming drug resistance. The complexes can induced apoptosis but did not affect mitochondria. The comparative DNA/protein binding studies of one of the most active pincer–(pseudo)dipeptide conjugates with the monoamino acid-based prototype revealed certain advantages of the former and gave further insights into the potential of this type of palladium-based antitumor agents. Dipeptides and dipeptide surrogates based on the functionalized picolinylamides combining S -donor amino acid residues with glycinate, alaninate, or phosphonate moieties readily undergo site-selective direct cyclopalladation. The resulting pincer–(pseudo)dipeptide conjugates display prominent cytotoxic properties, while the presence of the unbound amino acid residue facilitates the enhanced protein binding ability. [Display omitted] • Dipeptides and dipeptide surrogates are used as nonclassical pincer complexes. • Suggested combination of amino acids provides site-selective direct cyclopalladation. • Pincer–(pseudo)dipeptide conjugates exhibit prominent cytotoxic activity. • Resulting complexes can induce apoptosis but do not affect mitochondria. • Unbound amino acid residue facilitates enhanced protein binding ability of the complexes. [ABSTRACT FROM AUTHOR]