Metabolism of resveratrol in breast cancer cell lines: impact of sulfotransferase 1A1 expression on cell growth inhibition.
Resveratrol is a polyphenolic compound present in grapes and wine with anticancer activities that undergoes pronounced metabolism in humans. In order to determine whether metabolism of resveratrol also occurs in tumor cells and whether biotransformation has any impact on cytotoxicity, metabolism experiments were conducted with hormone-dependent ZR-75-1 and hormone-independent MB-MDA-231 human breast cancer cells. Along with resveratrol, it was possible to identify one metabolite, namely, resveratrol-3-O-sulfate in both cell lines. Its concentration in the cytoplasm and culture medium was 5.4- to 9-fold higher in ZR-75-1 cells than in MDA-MB-231 cells, concomitant with a 3.1-fold higher IC(50) value in the ZR-75-1 cell line (74 microM compared to 38 microM). By using RT-PCR, expression of sulfotransferase (SULT)1A1 mRNA, but not of other SULTs investigated, showed a close correlation with resveratrol 3-O-sulfate formation which was particularly high in ZR-75-1 and very low in MDA-MD-231 cells. In conclusion, we demonstrate that SULT1A1-based biotransformation reduces the anticancer activity of resveratrol in breast cancer cells, which must be considered in humans following oral uptake of dietary resveratrol as a chemopreventive agent.
Murias
Marek
M
Department of Clinical Pharmacy and Diagnostics, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
Miksits
Michaela
M
Aust
Sylvia
S
Spatzenegger
Margit
M
Thalhammer
Theresia
T
Szekeres
Thomas
T
Jaeger
Walter
W
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism*; D015239:Arylsulfotransferase / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D017931:DNA Primers; D006131:Growth Inhibitors; D012333:RNA, Messenger; D013267:Stilbenes; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; D000077185:Resveratrol