Chemistry and Biology of Moverastins, Inhibitors of Cancer Cell Migration, Produced by Aspergillus

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• 作者：Yasushi Takemoto ; Hidenori Watanabe ; Kenji Uchida ; Koji Matsumura ; Koichi Nakae ; Etsu Tashiro ; Kazutoshi Shindo ; Takeshi Kitahara and Masaya Imoto
• 刊名：Chemistry & Biology
• 出版年：2005
• 出版时间：December 2005
• 年：2005
• 卷：12
• 期：12
• 页码：1337-1347
• 全文大小：466 K

文摘

Summary

Cancer cell migration is a required step in cancer metastasis. We screened for inhibitors of cancer cell migration of microbial origin, and obtained moverastin, a member of the cylindrol family, from Aspergillus sp. F7720. However, the results of an NMR spectroscopic analysis raised the possibility that moverastin is a mixture of two diastereomers. Separation of the C-10 epimers of synthetic moverastin and a bioassay revealed that both diastereomers (moverastins A and B) had inhibitory effects on cell migration. Furthermore, we demonstrated that moverastins A and B inhibited FTase in vitro, and they also inhibited both the membrane localization of H-Ras and the activation of the PI3K/Akt pathway in EC17 cells. Thus, moverastins inhibited the migration of tumor cells by inhibiting the farnesylation of H-Ras, and subsequent H-Ras-dependent activation of the PI3K/Akt pathway.