Abstract 3760: A novel PKC-iota inhibitor, ICA-1 abrogates cell proliferation in breast cancer

Abstract

Abstract The objective of this research was to identify the efficacy of [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1) as a novel PKC-iota inhibitor in breast cell proliferation. PKC-α is highly overexpressed in human breast cancer and is localized depending on the trend of pathologic type of the tumor [Hum Pathol. (2008) 6:824-831]; however, little is understood about its role in regulating cell proliferation in breast cancer. Results showed that PKC-α was highly activated and overexpressed in MD-MB-468 breast cancer cells. PKC-α directly associated and phosphorylated Cdk7, a master cell cycle regulator at T170 in a cell cycle dependent manner, phosphorylating its downstream target, cdk2 at T160. PKC-α co-localized with Cdk7 in nuclear and cytoplasmic region of MD-MB-468 cells. PKC-α downregulation reduced Cdk7 phosphorylation following ICA-1 (10µM) as well as PKC-α silencing (by siRNA treatment). PKC-α knockdown inhibited overall proliferation in breast cancer cells suggesting that breast cancer cells may be proliferating through a PKC-α/Cdk7/cdk2 mediated pathway. Hence, our results emphasize the potential of ICA-1 as a novel PKC-α inhibitor and chemotherapeutic agent for breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3760. doi:1538-7445.AM2012-3760