Chemistry and biology of moverastins, inhibitors of cancer cell migration, produced by Aspergillus

Yasushi Takemoto, Hidenori Watanabe, Kenji Uchida, Koji Matsumura, Koichi Nakae, Etsu Tashiro, Kazutoshi Shindo, Takeshi Kitahara, Masaya Imoto

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1337-1347
Number of pages11
JournalChemistry and Biology
Volume12
Issue number12
DOIs
Publication statusPublished - 2005 Dec

Fingerprint

Aspergillus
Cell Movement
Cells
Phosphatidylinositol 3-Kinases
Neoplasms
Chemical activation
Prenylation
Spectroscopic analysis
Bioassay
Biological Assay
Tumors
Nuclear magnetic resonance
Neoplasm Metastasis
Membranes
moverastin A

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Chemistry and biology of moverastins, inhibitors of cancer cell migration, produced by Aspergillus. / Takemoto, Yasushi; Watanabe, Hidenori; Uchida, Kenji; Matsumura, Koji; Nakae, Koichi; Tashiro, Etsu; Shindo, Kazutoshi; Kitahara, Takeshi; Imoto, Masaya.

In: Chemistry and Biology, Vol. 12, No. 12, 12.2005, p. 1337-1347.

Research output: Contribution to journalArticle

Takemoto, Y, Watanabe, H, Uchida, K, Matsumura, K, Nakae, K, Tashiro, E, Shindo, K, Kitahara, T & Imoto, M 2005, 'Chemistry and biology of moverastins, inhibitors of cancer cell migration, produced by Aspergillus', Chemistry and Biology, vol. 12, no. 12, pp. 1337-1347. https://doi.org/10.1016/j.chembiol.2005.09.017
Takemoto, Yasushi ; Watanabe, Hidenori ; Uchida, Kenji ; Matsumura, Koji ; Nakae, Koichi ; Tashiro, Etsu ; Shindo, Kazutoshi ; Kitahara, Takeshi ; Imoto, Masaya. / Chemistry and biology of moverastins, inhibitors of cancer cell migration, produced by Aspergillus. In: Chemistry and Biology. 2005 ; Vol. 12, No. 12. pp. 1337-1347.
@article{29d91f4e378449f1a73bfadbba484732,
title = "Chemistry and biology of moverastins, inhibitors of cancer cell migration, produced by Aspergillus",
abstract = "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.",
author = "Yasushi Takemoto and Hidenori Watanabe and Kenji Uchida and Koji Matsumura and Koichi Nakae and Etsu Tashiro and Kazutoshi Shindo and Takeshi Kitahara and Masaya Imoto",
year = "2005",
month = "12",
doi = "10.1016/j.chembiol.2005.09.017",
language = "English",
volume = "12",
pages = "1337--1347",
journal = "Cell Chemical Biology",
issn = "2451-9448",
publisher = "Elsevier Inc.",
number = "12",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=28844473501&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28844473501&partnerID=8YFLogxK

U2 - 10.1016/j.chembiol.2005.09.017

DO - 10.1016/j.chembiol.2005.09.017

M3 - Article

C2 - 16356851

AN - SCOPUS:28844473501

VL - 12

SP - 1337

EP - 1347

JO - Cell Chemical Biology

JF - Cell Chemical Biology

SN - 2451-9448

IS - 12

ER -