The methoxylated flavones eupatorin and cirsiliol induce CYP1 enzyme expression in MCF7 cells.
Flavonoids have often been associated with cancer prevention and activity of the human cytochrome P450 enzymes CYP1A1 and CYP1B1 with the occurrence of cancer. The flavones eupatorin (1) and cirsiliol (2) enhanced CYP1 enzyme activity in a concentration-dependent manner in MCF7 human breast adenocarcinoma cells. In the range of 0-2.5 microM, 2 caused a dose-dependent increase in CYP1B1 mRNA levels and an increase in CYP1A1 mRNA. Compound 1 caused an increase in CYP1A1 and CYP1B1 mRNA at higher doses (approximately 5 microM). Both CYP1B1 and CYP1A1 catalyzed the conversion of 2 into an as yet unidentified compound. Application of the CYP1 family inhibitor, acacetin, significantly increased the IC(50) value of 2 in MCF7 cells, but did not significantly affect the action of 1. The data suggest that 2 induces CYP1 enzyme expression in cancer cells and is subsequently converted by CYP1B1 or CYP1A1 into an antiproliferative agent.
Androutsopoulos
Vasilis P
VP
Laboratory of Forensic Sciences and Toxicology, University of Crete, Heraklion, Voutes 71003, Greece. vasilis_androutsopoulos@yahoo.com
Li
Naichang
N
Arroo
Randolph R J
RR
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004354:Drug Screening Assays, Antitumor; D047309:Flavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D032410:Lantana / Q000737:chemistry; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis
D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D005419:Flavonoids; D012333:RNA, Messenger; C039824:cirsiliol; C103110:eupatorin; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1