Abstract 3441: Dynamin inhibitors as anticancer agent in cervical carcinoma.

Abstract

Abstract Dynamin is a 96 kDa GTPase enzyme involved in membrane constriction and fission during endocytosis. Among the three human dynamin genes, dynamin I is expressed in neurons and neuro-endocrine cells, dynamin II is expressed in most cell types, and dynamin III is strongly expressed in the testis, brain, and lung tissue. Dynamin II plays an essential role in the completion of the final stage of mitosis, cytokinesis. MiTMAB (myristyl trimethyl ammonium bromides) and OcTMAB (octadecyltrimethyl ammonium bromide) are small-molecule inhibitors of dynamin that competitively interfere with the ability of dynamin to bind phospholipids and prevent receptor-mediated endocytosis. In this study, we investigated whether dynamin inhibitor could inhibit survival, proliferation, and invasion of cervical cancer cell lines. To evaluate the role of dynamin II in cell proliferation, we performed MTT assays with Hela and SiHa cells after incubation with various doses of MiTMAB or OcTMAB. To confirm the apoptosis after MiTMAB and OcTMAB treatment, active caspase-3 ELISA and FACS were performed. And to identify the role of dynamin II in cell invasion, we evaluated the secretion of MMP-9 after dynamin II inhibitor treatment by ELISA assay. We found that MiTMAB and OcTMAB had a growth-inhibiting effect at 2 or 3 day after treatment in both cells. Active caspase-3 expression and Annexin V intensity were increased by MiTMAB and OcTMAB. And the secretion of MMP-9 was increased after dynamin II inhibitor treatment. MiTMAB and OcTMAB are the first compounds reported to exclusively block cytokinesis without affecting progression through any other stage of the cell cycle. Cytokinesis failure induces cell death. These data revealed that dynamin II modulates cancer cell survival, proliferation, and invasion and suggest that dynamin II could be a key target for new strategies in cervical cancer treatment. Citation Format: Jeong-Won Lee, Hye Kyung Jeon. Dynamin inhibitors as anticancer agent in cervical carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3441. doi:10.1158/1538-7445.AM2013-3441