Expression of sulfotransferases and sulfatases in human breast cancer: impact on resveratrol metabolism.
Resveratrol is a naturally occurring anticancer compound present in grapes and wine that undergoes pronounced metabolism in human intestine and liver. In order to determine whether resveratrol is also bio-transformed in human breast carcinoma, metabolism experiments were conducted in breast tumor and adjacent non-tumorous specimens from 13 patients. Resveratrol was metabolized in cytosolic tissue fractions to resveratrol-3-O-sulfate: the formation rates were up to 33.5-fold higher in cancer samples than in peritumoral tissue. Further quantitative real-time RT-PCR analysis revealed similar expression of sulfotransferases SULT1A2, 1A3, and 1E1 in the paired control and tumor tissues. Sulfotransferase SULT1A1 expression was below the detection limit in all samples. Interestingly, mRNA expression of steroid sulfatase STS, but not of arylsulfatases ARS-A and ARS-B, was significantly higher (p<0.0017) in non-malignant specimens than in tumor tissue samples, which might explain the higher resveratrol-3-O-sulfate concentrations in breast cancer specimens. Cellular localization of SULT1A3 and STS was also assessed by indirect immunofluorescence on paraffin-embedded sections from control and malignant breast tissue clearly showing a correlation of qRT-PCR data with protein expression of these two enzymes. Our data elucidate the metabolism of resveratrol in malignant and non-malignant breast tissue, which must be considered in humans after oral uptake of dietary resveratrol as a chemopreventive agent.
Miksits
Michaela
M
Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
Wlcek
Katrin
K
Svoboda
Martin
M
Thalhammer
Theresia
T
Ellinger
Isabella
I
Stefanzl
Gabriele
G
Falany
Charles N
CN
Szekeres
Thomas
T
Jaeger
Walter
W
D000368:Aged; D001192:Arylsulfatases / Q000235:genetics / Q000378:metabolism*; D015239:Arylsulfotransferase / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043266:Steryl-Sulfatase / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D013267:Stilbenes; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C403170:monoamine-sulfating phenol sulfotransferase; C020122:estrone sulfotransferase; D001192:Arylsulfatases; D043266:Steryl-Sulfatase; D000077185:Resveratrol