Abstract
Microcystins are cyclic heptapeptides produced by cyanobacteria. They potently inhibit the eukaryotic protein phosphatase families PP1 and PP2A. They are able to display toxicity only after transporter-mediated uptake by the cell. This uptake is mediated by the organic anion transporting polypeptides OATP1B1, OATP1B3, and OATP1A2. Liver cells express OATP1B1 and OATP1B3 transporters, which results in a pronounced liver toxicity of microcystins. However, OATP1B3 is also expressed in a significant percentage of hepatocellular carcinoma cells as well as gastrointestinal, lung, breast and colon tumors. Interestingly, compared to OATP1B1, OATP1B3 is found only in low abundance in liver cells. Thus selectivity that favors OATP1B3 over OATP1B1 should lead to a decreased hepatic clearance and toxicity, and an increased uptake in OATP1B3-expressing tumors, thus creating a therapeutic window for the respective compound.
Published Version
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