Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Eur J Pharmacol ; 939: 175456, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36528070

ABSTRACT

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.


Subject(s)
Breast Neoplasms , Lactones , Female , Humans , Orlistat/pharmacology , Orlistat/therapeutic use , Lactones/pharmacology , Breast Neoplasms/pathology , Cell Line, Tumor , Fatty Acids/metabolism , Lipids , Apoptosis , Cell Proliferation
2.
Eur J Pharmacol ; 910: 174466, 2021 Nov 05.
Article in English | MEDLINE | ID: mdl-34481879

ABSTRACT

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.


Subject(s)
Biological Products/pharmacology , Colonic Neoplasms/drug therapy , L-Amino Acid Oxidase/pharmacology , Viper Venoms/enzymology , Animals , Apoptosis/drug effects , Biological Products/isolation & purification , Biological Products/therapeutic use , Biotransformation/drug effects , Biotransformation/genetics , Cell Line, Tumor , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Crotalus , Drug Screening Assays, Antitumor , Gene Expression Regulation, Neoplastic/drug effects , Humans , L-Amino Acid Oxidase/isolation & purification , L-Amino Acid Oxidase/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL
...