Abstract 4546: COX-2 inhibitors arrest prostate cancer cell cycle progression by downregulation of kinetochore/centromere proteins

Abstract

Abstract Epidemiologic studies likewise revealed a decreased incidence of prostate cancer in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors. Previous in vitro studies have shown that inhibition of cyclooxygenase-2 (COX-2) arrests cancer cell growth. However, the molecular mechanism underlying the growth arrest effect of COX-2 inhibition remains elusive. In this study, we demonstrated that treatment with the COX-2 inhibitors celecoxib and CAY10404 significantly inhibited prostate cancer LNCaP cell proliferation. Flow cytometric analysis confirmed the cell cycle arrested at the G2/M phase and immunofluorescent staining indicated that inhibition of COX-2 prevented the cells from entering into mitosis. Further biochemical analysis showed that inhibition of COX-2 induced a dramatic down-regulation of key proteins in the kinetochore/centromere assembly, such as ZWINT, Cdc20, Ndc80, CENP-A, Bub1 and Plk1. Furthermore, the EP1 receptor antagonist SC51322 produced similar effects to the COX-2 inhibitors on LNCaP cell proliferation and down-regulation of kinetochore/centromere proteins, which did not occur in the EP2, EP3 and EP4 receptor antagonists, suggesting the COX-2 inhibitors arrest the cell proliferation and down-regulate kinetochore/centromere proteins through inactivation of the EP1 receptor. Our studies indicate that inhibition of COX-2 can arrest prostate cancer cell growth through inactivation of the EP1 receptor signaling and down-regulation of kinetochore / centromere proteins. Citation Format: Jared Bieniek, Chandra Childress, Matthew Swatski, Wannian Yang. COX-2 inhibitors arrest prostate cancer cell cycle progression by downregulation of kinetochore/centromere proteins. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4546. doi:10.1158/1538-7445.AM2014-4546