L-amino acid oxidase from snake venom: Biotransformation and induction of apoptosis in human colon cancer cells.
2021
Authors:
Nikodijević, Danijela D.Jovankić, Jovana V.
Cvetković, Danijela M.
Anđelković, Marko
Nikezić, Aleksandra G.
Milutinović, Milena G.
Document Type:
Article (Published version)
,
© 2021 Elsevier B.V.
Metadata
Show full item recordAbstract:
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.
Keywords:
ABC transporters; Anticancer; Drug resistance; Vipera ammodytesSource:
European Journal of Pharmacology, 2021, 910, 174466-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200378 (Institute of Information Technology) (RS-MESTD-inst-2020-200378)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200122 (University of Kragujevac, Faculty of Science) (RS-MESTD-inst-2020-200122)
DOI: 10.1016/j.ejphar.2021.174466
ISSN: 0014-2999
PubMed: 34481879
WoS: 000724575000005
Scopus: 2-s2.0-85114319134
URI
https://linkinghub.elsevier.com/retrieve/pii/S0014299921006208https://radar.ibiss.bg.ac.rs/handle/123456789/4481