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Tranilast Inhibits the Proliferation of Uterine Leiomyoma Cells in Vitro through G1 Arrest Associated with the Induction of p21^waf1 and p53

Department of Gynecology and Obstetrics (H.S., M.K., A.O., C.M., T.Ka., K.F., T.Ku., Y.T., K.T., S.F.), Kyoto University Graduate School of Medicine, Kyoto 606-8507; and Department of Obstetrics and Gynecology (T.N.), Shinshu University, School of Medicine, Matsumoto 390-8621, Japan

Address all correspondence and requests for reprints to: Shingo Fujii, M.D., Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shyogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: sfu{at}kuhp.kyoto-u.ac.jp.

Abstract

Uterine leiomyoma is a mesenchymal tumor composed of smooth muscle cells with fibrous tissues and many mast cells. Tranilast is known to suppress fibrosis or to work as a mast cell stabilizer and is reported to inhibit proliferation of vascular smooth muscle cells. In this study, we examined the effects of tranilast on cultured human leiomyoma cells in vitro to evaluate whether this agent has the potential to inhibit the growth of uterine leiomyomas. Tranilast inhibited the proliferation of cultured leiomyoma cells in a dose-dependent manner without any cytotoxic effect or induction of apoptosis. In association with the inhibitory effect, tranilast induced the cyclin-dependent kinase (CDK) inhibitor p21^waf1 and tumor suppressor gene p53 and decreased CDK2 activity. These results suggest that tranilast arrests the proliferation of uterine leiomyoma cells at the G0/G1 phase, through the suppression of CDK2 activity via an induction of p21^waf1 and p53. Tranilast was concluded to be a potent agent to inhibit proliferative activity of uterine leiomyoma cells.

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