Breast cancer as most often women's cancer is the second cause of mortality worldwide. Research interest increased in testing non-standard drugs to suppress breast cancer progression and become ...significant supplements in anticancer therapy. The anti-obesity drug Orlistat showed significant ability for modulation of cancer cell metabolism via antiproliferative, proapoptotic, antiangiogenic, antimetastatic, and hypolipidemic effects. The anticancer potential of Orlistat was evaluated by cytotoxicity (MTT assay), type of cell death (AO/EB double staining), determination of redox status parameters (superoxide, hydrogen peroxide, lipid peroxidation, reduced glutathione), and total lipid levels with colorimetric methods, as well on angiogenesis-related (VEGF, MMP-9, CXCR4/CXCL12) and fatty acid synthesis-related (ACLY, ACC, FASN) parameters on gene and protein levels (immunocytochemistry and qPCR). Based on obtained results Orlistat induces significant cytotoxic, proapoptotic, and anti-angiogenic effects in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells, without significant cytotoxic effects on normal MRC-5 cells. It decreased total lipid levels and changed redox status parameters and cancer cell metabolism via suppression of genes and proteins involved and fatty acid synthesis. Based on showed, Orlistat may be an important supplement in antiangiogenic therapy against breast cancer with no side effects on normal cells, making it a good candidate for future clinical trials.
This study evaluated the potential of antitumor activity of snake venom from Vipera ammodytes and L-amino acid oxidase from Crotalus adamanteus on different colorectal cancer cell lines through ...determination of cytotoxic activity by MTT assay, pro-apoptotic activity by acridine orange/ethidium bromide staining, and concentrations of redox status parameters (superoxide, reduced glutathione, lipid peroxidation) by colorimetric methods. The expression of genes involved in the biotransformation process and metabolite efflux was determined by qPCR method, while protein expression of glutathione synthetase and P-glycoprotein were analysed by immunocytochemistry. The analysis of cell death shows that snake venom dominantly leads cells to necrosis. Induction of apoptosis by L-amino acid oxidase was in correlation with oxidative disbalance in cancer cells. Gene expression profile of membrane transporters and CYP genes were different in each cell line and in correlation with their sensitivity of treatment. Our results show that L-amino acid oxidase from snake venom is a potent cytotoxic substance with pronounced pro-apoptotic activity. The inhibition of P-glycoprotein suggests that L-amino acid oxidase is a good substance for furter research of antitumor effect, with unexpressed potential for occurrence of drug resistance in vitro.
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•LAAO from Crotalus adamanteus venom is a proapoptotic agent.•The mechanism of their proapoptotic effect was mediated by changes in redox status.•LAAO change expression of genes involved in biotransformation processes.•Our in vitro results do not indicate the possibility of resistance occurrence.
The research aimed to optimize the ultrasound-assisted extraction of secondary metabolites and the antibacterial activity of the plant species Geranium robertianum. The phytochemical profiles of the ...optimized extracts, as well as their antibacterial and synergistic activity with an antibiotic and their potential mechanisms of action and cytotoxicity, were examined.
Response Surface Methodology was used to optimize extraction conditions. Optimized ethanol and acetone extracts were tested via microdilution, checkerboard, time-kill kinetics, and cell membrane permeability methods. The extracts displayed broad antibacterial activity with minimum inhibitory concentrations ranging from 1.25 to 20 mg ml-1. In addition, the extract synergistically reacted with gentamicin against gentamicin-resistant strains of Escherichia coli and Staphylococcus aureus, enhancing the efficacy of the antibiotic up to 32-fold. The extracts demonstrated strain-dependent bactericidal activity in a 24-h time interval. They increase the permeability of the cell membrane, thus disrupting its normal functioning. The cytotoxic concentration (CC50) on human keratinocytes was 1771.24 ± 5.78 µg ml-1 for ethanol extract, and 958.01 ± 6.14 µg ml-1 for acetone extract. Kaempferol, ellagic acid, quercetin, and rutin were recognized as the main components in both extracts.
The findings of this study indicate that the extracts of G. robertianum can be considered as potential natural antibacterial agents in the control of microorganisms.
Due to their promising effects, gold(III) complexes recently drew increasing attention in the design of new metal-based anticancer therapeutics. Two gold(III) complexes, square-planar Au(DPP)Cl2+ - ...Complex 1 and distorted square-pyramidal Au(DMP)Cl3 - Complex 2 (where DPP=4,7-diphenyl-1,10-phenanthroline and DMP=2,9-dimethyl-1,10-phenanthroline) were previously synthetized, described and approved as complexes with pronounced cytotoxic effects on colorectal HCT-116 and breast MDA-MB-231 cancer cells. This study investigated the type of cell death by AO/EB double staining, and identification of possible targets responsible for their cytotoxicity, monitored by immunofluorescence and qPCR methods. Both complexes induced apoptosis in all applied concentrations. In the HCT-116 cells apoptosis was activated by external apoptotic pathway, via increase of Fas receptor protein expression and Caspase 8 gene expression. Also, the mitochondrial pathway was triggered by affecting the Bcl-2 members of regulatory proteins and increased caspase 9 protein expression. In MDA-MB-231 cells, apoptosis was initiated from the mitochondria, due to disbalance between expressions of pro- and anti-apoptotic Bcl-2 family members and caspase 9 activation. Complex 1 shows better activity compared to Complex 2, which is in accordance with its structural characteristics. The results deal weighty data about proapoptotic activity of gold(III) complexes and highlighted potential targets for cancer therapy.
are widely present in many environments related to humans, including the human body and the food that they consume, from both plant or animal origin. Hence, they are considered relevant members of ...the gastrointestinal tract microbiota. On the other hand, these bacteria are also recognized as putative pathogens, able to impair human health and, in food, they are considered indicators for the microbiological quality and hygiene status of a production process. Nevertheless, beneficial properties have also been associated with
, such as the ability to synthesize peptides and proteins, which can have a role in the structure of microbial communities. Among these antimicrobial molecules, those with higher molecular mass are called colicins, while those with lower molecular mass are named microcins. In recent years, some studies show an emphasis on molecules that can help control the development of pathogens. However, not enough data are available on this subject, especially related to microcins. Hence, this review gathers and summarizes current knowledge on colicins and microcins, potential usage in the treatment of pathogen-associated diseases and cancer, as well as putative applications in food biotechnology.
Teucrum chamaedrys L. is one of the known medicinal plants, useful for treatment of various health problems, especially digestive. In this study, we investigated methanol, ethyl-acetate and acetone ...extracts of T. chamaedrys in respect to their anticancer properties in SW480 colorectal cancer cells.
Cytotoxicity and proapoptotic potential were assessed by MTT cell viability assay and AO/EB double staining. Molecular mechanisms of induced apoptosis were determined by monitoring Fas receptor protein expression through immunofluorescence, Caspase 8 and 9 activity, as well as concentrations of O2.- spectrophotometrically. Additionally, mRNA expression of biotransformation enzymes (CYP1A1, CYP1B1, GSTP1) and membrane transporters (MRP1 and MRP2) involved in drug resistance were investigated by qPCR method. Qualitative analysis of individual phenolic compounds was performed by reversed phase HPLC-MS analysis.
Methanol extract shows the best cytotoxicity and selectivity compared to ethyl-acetate and acetone extracts, mainly causing apoptosis of SW480 cells, without affecting normal HaCaT keratinocytes. The increased expression of Fas receptor protein and caspase 8 activity indicate that the death receptor-mediated pathway plays a crucial role in the observed apoptosis. The increased caspase 9 activity and O2.- concentration suggest that mitochondria are also involved in the apoptosis. T. chamaedrys methanol extract inhibits mRNA expression of CYP1A1, CYP1B1, GSTP1, MRP1 and MRP2 in SW480 cells.
Induction of apoptosis and inhibition of CYP1A1, CYP1B1, GSTP1, MRP1 and MRP2 mRNA expression implies that T. chamaedrys can serve as a valuable source of bioactive compounds as dietary supplements or selective anticancer agents, with the ability to induce apoptosis and modulate drug resistance in colorectal cancer cells.
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To study the effects of electroporation on different cell lines.
The effects of electroporation on human breast cancer (MDA-MB-231), human colon cancer (SW-480 and HCT-116), human fibroblast cell ...line (MRC-5), primary human aortic smooth muscle cells (hAoSMC) and human umbilical vein endothelial cells (HUVEC) were studied. Real-time technology was used for cell viability monitoring. Acridine orange/ethidium bromide assay was applied for cell death type determination. A numerical model of electroporation has been proposed.
Electroporation induced inhibition of cell viability on dose (voltage) dependent way. The electroporation treatment 375–437.5Vcm−1 caused irreversible electroporation of cancer cells and reversible electroporation of healthy cells. The application of lower voltage rating (250Vcm−1) led to apoptosis as the predominant type of cell death, whereas the use of higher voltage (500Vcm−1) mainly caused necrosis.
Electroporation represents a promising method in cancer treatment. Different cancer cell lines had different response to the identical electroporation treatment. Electroporation 375–437.5Vcm−1 selectively caused permanent damage of cancer cells (SW-480), while healthy cells (MRC-5, hAoSM and HUVEC) recovered after 72h. The type of cell death is dependent of electroporation conditions. The proposed numerical model is useful for the analysis of phenomena related to electroporation treatment.
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•Electroporation is a promising modality in cancer treatment.•Cell lines have different responses to identical electroporation treatment.•RTCA technology is useful for cell viability monitoring after electroporation.•The type of cell death is dependent on electroporation conditions.•A numerical model is useful for investigating phenomena related to electroporation.
•Salvia amplexicaulis extracts were analyzed for composition and biological effects.•The extracts contained phenolic acids and flavonoids, mainly kaempferol glycosides.•Water, methanol and ethanol ...extracts performed the strongest antioxidant activity.•Water extract was stronger in antifungal and cytotoxic assays than ethanol extract.•Ethanol extract showed stronger antibacterial and antineurodegenerative effects.
This study was aimed to examine chemical composition and biological activities of water, ethanol, methanol, ethyl acetate and dichloromethane extracts of Salvia amplexicaulis Lam. (Lamiaceae). The high performance liquid chromatography (HPLC) analysis showed that the largest amounts of polyphenols were present in methanol extract, followed by ethanol and water extracts, with the kaempferol glycosides as the most abundant components (>40%). Water extract was the most powerful in 2.2-dyphenyl-1-picrylhydrazyl (DPPH), ferric-reducing ability of plasma (FRAP) and β-carotene bleaching antioxidant assays, while the ethanol extract performed the highest activity in 2.2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS) assay. Methanol and water extracts neutralized DPPH radicals more efficiently than standard 3.5-di-tert-butyl-4 hydroxytoluene (BHT) (15.1μg/mL, 15.8μg/mL and 17.9μg/mL, respectively). The antioxidant activity could be possibly attributed to very high content of kaempferol glycosides in the extracts. Ethanol extract was more active against pathogenic bacteria (minimum inhibitory concentrations, MIC, ranged between 30.0mg/mL and 40.0mg/mL) than water extract, which was generally stronger antifungal agent (MIC varied from 8.0mg/mL to 64.0mg/mL). Water extract also showed stronger cytotoxic activity against HCT-116 cells than ethanol extract (IC50 values were 114.1μg/mL and 164.5μg/mL, respectively). The ethanol extract showed slightly stronger antineurodegenerative effects than water extract, especially in tyrosinase inhibition where ethanol extract was considerably effective compared with commercial inhibitor kojic acid. Ethanol and water extracts of S. amplexicaulis showed strong antioxidant and antineurodegenerative activities, which places them among promising natural curative resources for food and pharmaceutical industries.
To elucidate an antitumor drug exhibiting enhanced activity relative to cisplatin, a novel dinuclear gold(III) complex was synthesized, incorporating 1,5-naphthyridine as a bridging ligand. ...Subsequently, the newly synthesized complex underwent comprehensive characterization using various techniques to validate its structural attributes. The stability of the complex in both water and PBS buffer was assessed through UV–Vis spectroscopy. DNA binding studies were conducted employing UV–Vis, fluorescence spectroscopy, and viscosity measurements. Competitive studies with ethidium bromide (EB) or 4′-hydroxyethidium (HOE) were performed utilizing fluorescence spectroscopy. The findings indicated that the dinuclear gold(III) complex interacts with calf thymus DNA (CT-DNA) through a groove binding mode. Moreover, the investigated complex exhibited significant binding constants for its interaction with human serum albumin (HSA) and bovine serum albumin (BSA) and interactions in the presence of site markers (eosin Y or ibuprofen). The dinuclear gold(III) complex demonstrated notable cytotoxicity against HCT116 and MDA-MB-231 cancer cell lines at 24 and 72 h post-treatment. Furthermore, the complex displayed selectivity by inducing significantly lower cytotoxic activity in healthy cells than in cancerous ones. In support of its antitumor activity, the complex exhibited proapoptotic effects, as evidenced by increased caspase 9 activity and low percentages of necrosis. Molecular docking simulations were employed to corroborate all experimentally obtained results.
