The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1.
Resveratrol is a cancer preventative agent that is found in red wine. Piceatannol is a closely related stilbene that has antileukaemic activity and is also a tyrosine kinase inhibitor. Piceatannol differs from resveratrol by having an additional aromatic hydroxy group. The enzyme CYP1B1 is overexpressed in a wide variety of human tumours and catalyses aromatic hydroxylation reactions. We report here that the cancer preventative agent resveratrol undergoes metabolism by the cytochrome P450 enzyme CYP1B1 to give a metabolite which has been identified as the known antileukaemic agent piceatannol. The metabolite was identified by high performance liquid chromatography analysis using fluorescence detection and the identity of the metabolite was further confirmed by derivatisation followed by gas chromatography-mass spectrometry studies using authentic piceatannol for comparison. This observation provides a novel explanation for the cancer preventative properties of resveratrol. It demonstrates that a natural dietary cancer preventative agent can be converted to a compound with known anticancer activity by an enzyme that is found in human tumours. Importantly this result gives insight into the functional role of CYP1B1 and provides evidence for the concept that CYP1B1 in tumours may be functioning as a growth suppressor enzyme.
Potter
G A
GA
Cancer Drug Discovery Group, School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK. gapotter@dmu.ac.uk
Patterson
L H
LH
Wanogho
E
E
Perry
P J
PJ
Butler
P C
PC
Ijaz
T
T
Ruparelia
K C
KC
Lamb
J H
JH
Farmer
P B
PB
Stanley
L A
LA
Burke
M D
MD
D000970:Antineoplastic Agents / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism* / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases; D018890:Chemoprevention; D002851:Chromatography, High Pressure Liquid; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000517:prevention & control; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014920:Wine
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D000077185:Resveratrol