L-amino acid oxidase from snake venom: Biotransformation and induction of apoptosis in human colon cancer cells.
2021
Аутори:
Nikodijević, Danijela D.Jovankić, Jovana V.
Cvetković, Danijela M.
Anđelković, Marko
Nikezić, Aleksandra G.
Milutinović, Milena G.
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2021 Elsevier B.V.
Метаподаци
Приказ свих података о документуАпстракт:
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.
Кључне речи:
ABC transporters; Anticancer; Drug resistance; Vipera ammodytesИзвор:
European Journal of Pharmacology, 2021, 910, 174466-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-200007)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200378 (Институт за информационе технологије, Крагујевац) (RS-200378)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200122 (Универзитет у Крагујевцу, Природно-математички факултет) (RS-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