NYMC Faculty Publications
Mechanisms of Ceramide-Induced COX-2-Dependent Apoptosis in Human Ovarian Cancer OVCAR-3 Cells Partially Overlapped With Resveratrol
Author Type(s)
Faculty
DOI
10.1002/jcb.24539
Journal Title
Journal of Cellular Biochemistry
First Page
1940
Last Page
1954
Document Type
Article
Publication Date
8-1-2013
Department
Biochemistry and Molecular Biology
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 of caspase-3 and -7 are observed. However, a p38 kinase-dependent signal transduction pathway and change in mitochondrial potential are also involved in ceramide-induced apoptosis.
Recommended Citation
Lin, H., Delmas, D., Vang, O., Hsieh, T., Lin, S., Cheng, G., Chiang, H., Chen, C., Tang, H., Crawford, D., Whang-Peng, J., Hwang, J., Liu, L., & Wu, J. M. (2013). Mechanisms of Ceramide-Induced COX-2-Dependent Apoptosis in Human Ovarian Cancer OVCAR-3 Cells Partially Overlapped With Resveratrol. Journal of Cellular Biochemistry, 114 (8), 1940-1954. https://doi.org/10.1002/jcb.24539
