Ceramide induces COX‐2‐dependent induction of apoptosis in human ovarian cancer OVCAR‐3 cells by mechanisms that partially overlap with actions of resveratrol

Abstract
Ceramide is a member of the sphingolipid family of bioactive molecules demonstrated to have profound, diverse biological activities. Ceramide is a potential chemotherapeutic agent via the induction of apoptosis. Exposure to ceramide activates extracellular‐signal‐regulated kinases (ERK)1/2‐ and p38 kinase‐dependent apoptosis in human ovarian cancer OVCAR‐3 cells, concomitant with an increase in the expression of COX‐2 and p53 phosphorylation. Blockade of cyclooxygenase‐2 (COX‐2) activity by siRNA or NS398 correspondingly inhibited ceramide‐induced p53 Ser‐15 phosphorylation and apoptosis; thus COX‐2 appears at the apex of the p38 kinase‐mediated signaling cascade induced by ceramide. Induction of apoptosis by ceramide or resveratrol was inhibited by the endocytosis inhibitor, cytochalasin D (CytD); however, cells exposed to resveratrol showed greater sensitivity than ceramide‐treated cells. Ceramide‐treated cells underwent a dose‐dependent reduction in trans‐membrane potential. Although both ceramide and resveratrol induced the expressions of caspase‐3 and ‐7, the effect of inducible COX‐2 was different in caspase‐7 expression induced by ceramide compared to resveratrol. In summary, resveratrol and ceramide converge on an endocytosis‐requiring, ERK1/2‐dependent signal transduction pathway and induction of COX‐expression as an essential molecular antecedent for subsequent p53‐dependent apoptosis. In addition, expressions...

Source: Journal of Cellular Biochemistry - March 13, 2013 Category: Biochemistry Authors: Hung‐Yun Lin, Dominique Delmas, Ole Vang, Tze‐Chen Hsieh, Sharon Lin, Guei‐Yun Cheng, Hsiao‐Ling Chiang, Chiao En Chen, Heng‐Yuan Tang, Dana R. Crawford, Jacqueline Whang‐Peng, Jaulang Hwang, Leroy F. Liu, Joseph M. Wu Tags: Article Source Type: research