TY - JOUR
T1 - Chemistry and biology of moverastins, inhibitors of cancer cell migration, produced by Aspergillus
AU - Takemoto, Yasushi
AU - Watanabe, Hidenori
AU - Uchida, Kenji
AU - Matsumura, Koji
AU - Nakae, Koichi
AU - Tashiro, Etsu
AU - Shindo, Kazutoshi
AU - Kitahara, Takeshi
AU - Imoto, Masaya
N1 - Funding Information:
The authors are grateful to Dr. M. Matsumoto (Chugai Pharmaceutical Co. LTD) for the gift of ascochlorin. They also thank Dr. K. Dobashi (Mercian Co. LTD) for fermentation and taxonomic study of the produced strain. This study was partly supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chembiol.2005.09.017
DO - 10.1016/j.chembiol.2005.09.017
M3 - Article
C2 - 16356851
AN - SCOPUS:28844473501
SN - 2451-9448
VL - 12
SP - 1337
EP - 1347
JO - Cell Chemical Biology
JF - Cell Chemical Biology
IS - 12
ER -
