Pyrimethamine exerts significant antitumor effects on human ovarian cancer cells both in vitro and in vivo

Pyrimethamine has been used principally to treat infections from protozoan parasites. Although previous studies have shown that pyrimethamine exhibited anticancer activity by inducing cellular apoptosis, there are none that show that pyrimethamine possesses anticancer activity with respect to ovarian cancer. We examined the roles of pyrimethamine on apoptosis and proliferation, DNA damage, and cell cycle distribution of human ovarian cancer cell lines in vitro. To investigate the antitumor efficacy of pyrimethamine in vivo, we established two intraperitoneal ovarian carcinoma models in nude mice. Pyrimethamine significantly induced apoptosis of ovarian cancer cells via growth inhibition, cell cycle arrest, and nuclear DNA damage in vitro and manifested antitumor activity by inhibiting tumor growth, thereby prolonging the survival time of tumor-bearing mice. We also demonstrated that pyrimethamine increased the expression of caspase-9 and decreased the expression of X-linked inhibitor of apoptosis protein. In conclusion, the antitumor effects of pyrimethamine were associated with enhanced apoptosis of tumor cells and inhibition of the growth of intratumoral microvessels. Our results indicate that pyrimethamine may provide an effective approach toward inhibiting the growth of ovarian cancer with minimal adverse effects. *Ya Liu and Tao Yi contributed equally to the writing of this article. Correspondence to Hongjing Wang, PhD, Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, No. 20, Section 3, South People's Road, Chengdu, Sichuan 610041, People's Republic of China Tel: +86 028 855 01211; fax: +86 028 855 02822; e-mail: whjscdx@163.com Received July 18, 2018 Accepted December 10, 2018 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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