IN VITRO EFFECT OF NATURAL EXTRACTS ON THE CATALYTIC ACTIVITY OF CYTOCHROME P450 AND IDENTIFYING OF MUTATIONS IN CYPlBl SEQUENCE OF LUNG CANCER CELLS

Abstract

Major P450 enzymes involved in the detoxication and activation of a number of environmental procarcinogens including CYP3A4, CYPlBI, CYPIAI, CYPIA2 ... Therefore, a potential mechanism by which natural extracts protect cell against tumorigenesis by enhancing the catalytic activity of bioactivating CYP enzymes. In addition to catalyzing toxicant bioactivation, CYP enzymes also metabolize clinically useful therapeutic agents. Hence, it is important to examine the interaction between naturals extracts compound and P450 enzymes not only because this herbal medicine may confer chemoprotection in chemical carcinogenesis but also because the concomitant ingestion of naturals extracts compound and conventional drugs may result in herb-drug interaction. In the present study. we investigated the in vitro effect of natural extracts on the catalytic activity of CYP. Our results indicate that natural extracts inhibits CYP content and increases activity. Moreover. the occurrence of genetic polymorphisms in the CYPIBI genes was determined. One type of CYPIBI polymorphism has been investigated in lung cancer cells, namely m3-type which corresponds to nucleotide changes at A 1358G leading to an Asn453Ser exchange was studied