Protein tyrosine phosphatase 1B inhibitory properties of seco-cucurbitane triterpenes obtained from fruiting bodies of Russula lepida
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The known seco-cucurbitane triterpene, (24E)-3,4-seco-cucurbita-4,24-diene-3,26,29-trioic acid (1), has been isolated as a potent protein tyrosine phosphatase (PTP) 1B inhibitor together with a new analogue, (24E)-3,4-seco-cucurbita-4,24-diene-3-hydroxy-26,29-dioic acid (2), from the fruiting bodies of Russula lepida. Further evaluation of their biological properties against PTPs revealed that compound 1 inhibited T-cell PTP activity similarly to PTP1B and exhibited moderate selectivity against PTP1B over vaccinia H-1-related phosphatase. Moreover, the in vitro growth inhibitory effects of 1 and 2 against three human cancer cell lines were examined in order to evaluate cell-based efficacy. However, neither 1 nor 2 enhanced insulin-stimulated p-Akt levels at non-cytotoxic concentrations.
Keywords(24E)-3,4-Seco-cucurbita-4,24-diene-3,26,29-trioic acid Seco-cucurbitane triterpene Russula lepida Protein tyrosine phosphatase 1B Inhibitor
This work was supported in part by a Grant-in-Aid for Scientific Research (25870660 and 16K21310) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan to H.Y. and the Takeda Science Foundation to H.Y. We are grateful to the Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University for providing the human cancer cell lines.
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