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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: METHODS, RESULTS. Meshes: Animals, Biological Transport, Breast Neoplasms, CHO Cells, Cell Line, Tumor, Cricetulus, Female, Gene Knockdown Techniques, Glucuronides, Liver-Specific Organic Anion Transporter 1, Organic Anion Transporters, Organic Anion Transporters, Sodium-Independent, Resveratrol, Rifampin, Solute Carrier Organic Anion Transporter Family Member 1B3, Stilbenes.
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Are resveratrol and its major sulfated conjugates substrates of organic anion transporting polypeptides ( OATPs ) : impact on growth of ZR-75-1 breast cancer cells? Context: Resveratrol is a naturally occurring polyphenolic compound with various pharmacological activities. These effects are observed despite its low bioavailability, which is particularly caused by extensive phase II metabolism. It is unknown whether resveratrol and its metabolites can accumulate to bioactive levels in organs and tissues through protein-mediated transport mechanisms. Because organic anion transporting polypeptides (OATPs) mediate the uptake of many clinically important drugs, we investigated their role in the cellular transport of resveratrol and its major glucuronides and sulfates. Uptake experiments were performed with resveratrol and its glucuronides and sulfates in OATP-expressing Chinese hamster ovary (CHO) and breast cancer (ZR-75-1) cells. The uptake rates for resveratrol in OATP1B1-, OATP1B3-, and OATP2B1-transfected Chinese hamster ovary cells were four- to sixfold higher compared to wild-type cells. Resveratrol-3-O-4'-O-disulfate was transported by OATP1B1 and OATP1B3, while resveratrol-3-O-sulfate was exclusively transported by OATP1B3. However, resveratrol-4'-O-sulfate, resveratrol-3-O-glucuronide, and resveratrol-4'-O-glucuronide did not show any affinity for these OATPs. OATP-dependent uptake of resveratrol was also confirmed in ZR-75-1 cells.
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Our data revealed that OATPs act as cellular uptake transporters for resveratrol and its major sulfates, which must be considered in humans following oral uptake of dietary resveratrol. Final Decision: yes