Polycyclic aromatic hydrocarbon-induced CYP1B1 activity is suppressed by perillyl alcohol in MCF-7 cells.
Perillyl alcohol (POH) is a dietary monoterpene with potential applications in chemoprevention and chemotherapy. Although clinical trials are under way, POH's physiological and pharmacological properties are still unclear. In the present study, the effect of POH on polycyclic aromatic hydrocarbon (PAH)-induced genotoxicity, and the related expression were examined in MCF-7 cells. Exposure to environmental toxicant increases the risk of cancer. Many of these compounds are pro-carcinogens and are biotransformed into their ultimate genotoxic structures by xenobiotic metabolizing enzymes. CYP1A1 and 1B1 are enzymes that catalyze the biotransformation of dimethylbenz[a]anthracene (DMBA). Our data revealed that 0.5 microM of POH was effective in blocking DMBA-DNA binding. Ethoxyresorufin-O-deethylase (EROD) assay indicated that the administration of POH inhibited the DMBA-induced enzyme activity in MCF-7 cells. Enzyme kinetic analysis revealed that POH inhibited CYP1B1 but not CYP1A1 activity. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay also demonstrated that the monoterpene reduced CYP1B1 mRNA abundance induced by DMBA. The present study illustrated that POH might inhibit and downregulate CYP1B1, which could protect against PAH-induced carcinogenesis.
Chan
Nelson L S
NL
Department of Biochemistry, The Chinese University of Hong Kong, Rm. 507C MMW Bldg., Shatin, N.T., Hong Kong.
Wang
Huan
H
Wang
Yun
Y
Leung
Hau Yi
HY
Leung
Lai K
LK
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000970:Antineoplastic Agents / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D018736:DNA Adducts / Q000037:antagonists & inhibitors*; D004249:DNA Damage / Q000502:physiology; D015536:Down-Regulation; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D039821:Monoterpenes / Q000494:pharmacology*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D015533:Transcriptional Activation / Q000187:drug effects; D015262:Xenobiotics / Q000633:toxicity
D000970:Antineoplastic Agents; D002273:Carcinogens; D018736:DNA Adducts; D004791:Enzyme Inhibitors; D039821:Monoterpenes; D011084:Polycyclic Aromatic Hydrocarbons; D015262:Xenobiotics; C032208:perillyl alcohol; D015127:9,10-Dimethyl-1,2-benzanthracene; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1