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Geranylgeranylacetone inhibits lysophosphatidic acid-induced invasion of human ovarian carcinoma cells in vitro
Article first published online: 28 FEB 2005
Copyright © 2005 American Cancer Society
Volume 103, Issue 7, pages 1529–1536, 1 April 2005
How to Cite
Hashimoto, K., Morishige, K.-i., Sawada, K., Tahara, M., Shimizu, S., Sakata, M., Tasaka, K. and Murata, Y. (2005), Geranylgeranylacetone inhibits lysophosphatidic acid-induced invasion of human ovarian carcinoma cells in vitro. Cancer, 103: 1529–1536. doi: 10.1002/cncr.20941
- Issue published online: 18 MAR 2005
- Article first published online: 28 FEB 2005
- Manuscript Accepted: 3 DEC 2004
- Manuscript Revised: 24 NOV 2004
- Manuscript Received: 30 SEP 2004
- Ministry of Education, Science, Sports and Culture of Japan
- lysophosphatidic acid;
- ovarian carcinoma
Lysophosphatidic acid (LPA) induced a dose-dependent increase of cancer cell invasion by promoting Rho/Rho-associated kinase signaling. Prenylation of Rho is essential for regulating cell growth, motility, and invasion. Geranylgeranylacetone (GGA), an isoprenoid compound, is used clinically as an antiulcer drug. Recent findings suggested that GGA might inhibit the small GTPase activation by suppressing prenylation. The authors hypothesized that the anticancer effects of GGA result from the inhibition of Rho activation.
The authors examined the effect of GGA using an in vitro invasion assay in human ovarian carcinoma cells, and analyzed the mechanism of the GGA effect on Rho activation, stress fiber formation and focal adhesion assembly, which are essential processes for cell invasion.
The induction of ovarian carcinoma cell invasion by LPA was inhibited by the addition of GGA in a dose-dependent manner. Treatment of cancer cells with GGA resulted in inactivation of Rho, changes in cell morphology, loss of stress fiber formation and focal adhesion assembly, and the suppression of tyrosine phosphorylation of focal adhesion proteins. The effect of GGA on cancer cells was partially prevented by the addition of geranylgeraniol, which is an intermediate of geranylgeranyl pyrophosphate and compensates geranylgeranylation of Rho.
The inhibition of LPA-induced invasion by GGA was, at least in part, derived from suppressed Rho activation by preventing geranylgeranylation. Cancer 2005. © 2005 American Cancer Society.