This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, M. Articles by Xu, X.-C. Search for Related Content PubMed PubMed Citation Articles by Li, M. Articles by Xu, X.-C.

Induction of Apoptosis in Colon Cancer Cells by Cyclooxygenase-2 Inhibitor NS398 through a Cytochrome c-dependent Pathway¹

Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown cancer preventive activity in patients who took them frequently. These drugs can induce tumor cells to undergo apoptosis in vitro. NS398, a cyclooxygenase-2 (COX-2)-selective inhibitor, has been reported to cause apoptosis in cancer cell lines. Therefore, we examined its effect on 15 human colon cancer cell lines and investigated its mechanism of action. NS398 decreased cell viability in all of the cell lines. Tumor cells that expressed COX-2 were shown to be more sensitive to NS398 treatment. In three selected colon cancer cell lines, NS398-induced apoptosis was mediated by the release of cytochrome c from mitochondria and, consequently, by the activation of caspase-9 and caspase-3 and by the cleavage of poly(ADP-ribose) polymerase. In contrast, caspase-8 was not involved in NS398-induced apoptosis, which suggested that the cytochrome c pathway may play an important role in NS398-induced apoptosis in colon cancer cell lines. Therefore, the combination of NS398 with apoptosis-inducing drugs through cytochrome c-independent pathways may be warranted.

This article has been cited by other articles:

				A. Hoque, H. Chen, and X.-c. Xu Statin Induces Apoptosis and Cell Growth Arrest in Prostate Cancer Cells Cancer Epidemiol. Biomarkers Prev., January 1, 2008; 17(1): 88 - 94. [Abstract] [Full Text] [PDF]

				A. Jimeno, M. L. Amador, P. Kulesza, X. Wang, B. Rubio-Viqueira, X. Zhang, A. Chan, J. Wheelhouse, H. Kuramochi, K. Tanaka, et al. Assessment of celecoxib pharmacodynamics in pancreatic cancer Mol. Cancer Ther., December 1, 2006; 5(12): 3240 - 3247. [Abstract] [Full Text] [PDF]

				M. C. Ralstin, E. A. Gage, M. T. Yip-Schneider, P. J. Klein, E. A. Wiebke, and C. M. Schmidt Parthenolide Cooperates with NS398 to Inhibit Growth of Human Hepatocellular Carcinoma Cells through Effects on Apoptosis and G0-G1 Cell Cycle Arrest Mol. Cancer Res., June 1, 2006; 4(6): 387 - 399. [Abstract] [Full Text] [PDF]

				G. Gasparini, D. Gattuso, A. Morabito, R. Longo, F. Torino, R. Sarmiento, S. Vitale, T. Gamucci, and L. Mariani Combined Therapy with Weekly Irinotecan, Infusional 5-Fluorouracil and the Selective COX-2 Inhibitor Rofecoxib Is a Safe and Effective Second-Line Treatment in Metastatic Colorectal Cancer Oncologist, October 1, 2005; 10(9): 710 - 717. [Abstract] [Full Text] [PDF]

				M. E. Winters, A. I. Mehta, E. F. Petricoin III, E. C. Kohn, and L. A. Liotta Supra-additive Growth Inhibition by a Celecoxib Analogue and Carboxyamido-triazole Is Primarily Mediated through Apoptosis Cancer Res., May 1, 2005; 65(9): 3853 - 3860. [Abstract] [Full Text] [PDF]

				R. C.K. Panguluri, L. O. Long, W. Chen, S. Wang, A. Coulibaly, F. Ukoli, A. Jackson, S. Weinrich, C. Ahaghotu, W. Isaacs, et al. COX-2 gene promoter haplotypes and prostate cancer risk Carcinogenesis, June 1, 2004; 25(6): 961 - 966. [Abstract] [Full Text] [PDF]

				T. G. Tessner, F. Muhale, S. Schloemann, S. M. Cohn, A. R. Morrison, and W. F. Stenson Ionizing radiation up-regulates cyclooxygenase-2 in I407 cells through p38 mitogen-activated protein kinase Carcinogenesis, January 1, 2004; 25(1): 37 - 45. [Abstract] [Full Text] [PDF]

				H. Nishihara, S. Kizaka-Kondoh, P. A. Insel, and L. Eckmann Inhibition of apoptosis in normal and transformed intestinal epithelial cells by cAMP through induction of inhibitor of apoptosis protein (IAP)-2 PNAS, July 22, 2003; 100(15): 8921 - 8926. [Abstract] [Full Text] [PDF]

				Y. Miyata, S. Koga, S. Kanda, M. Nishikido, T. Hayashi, and H. Kanetake Expression of Cyclooxygenase-2 in Renal Cell Carcinoma: Correlation with Tumor Cell Proliferation, Apoptosis, Angiogenesis, Expression of Matrix Metalloproteinase-2, and Survival Clin. Cancer Res., May 1, 2003; 9(5): 1741 - 1749. [Abstract] [Full Text] [PDF]

				H. A. Minter, J. W. Eveson, S. Huntley, D. J. E. Elder, and A. Hague The Cyclooxygenase 2-selective Inhibitor NS398 Inhibits Proliferation of Oral Carcinoma Cell Lines by Mechanisms Dependent and Independent of Reduced Prostaglandin E2 Synthesis Clin. Cancer Res., May 1, 2003; 9(5): 1885 - 1897. [Abstract] [Full Text] [PDF]

				R. J. Levitt and M. Pollak Insulin-like Growth Factor-I Antagonizes the Antiproliferative Effects of Cyclooxygenase-2 Inhibitors on BxPC-3 Pancreatic Cancer Cells Cancer Res., December 15, 2002; 62(24): 7372 - 7376. [Abstract] [Full Text] [PDF]

				Y. Sun, X. M. Tang, E. Half, M. T. Kuo, and F. A. Sinicrope Cyclooxygenase-2 Overexpression Reduces Apoptotic Susceptibility by Inhibiting the Cytochrome c-dependent Apoptotic Pathway in Human Colon Cancer Cells Cancer Res., November 1, 2002; 62(21): 6323 - 6328. [Abstract] [Full Text] [PDF]

				A. Gugliucci, L. Ranzato, L. Scorrano, R. Colonna, V. Petronilli, C. Cusan, M. Prato, M. Mancini, F. Pagano, and P. Bernardi Mitochondria Are Direct Targets of the Lipoxygenase Inhibitor MK886. A STRATEGY FOR CELL KILLING BY COMBINED TREATMENT WITH MK886 AND CYCLOOXYGENASE INHIBITORS J. Biol. Chem., August 23, 2002; 277(35): 31789 - 31795. [Abstract] [Full Text] [PDF]

				R. Yamazaki, N. Kusunoki, T. Matsuzaki, S. Hashimoto, and S. Kawai Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Association with Activation of Peroxisome Proliferator-Activated Receptor gamma in Rheumatoid Synovial Cells J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 18 - 25. [Abstract] [Full Text] [PDF]

				A. Murakami, D. Takahashi, T. Kinoshita, K. Koshimizu, H. W. Kim, A. Yoshihiro, Y. Nakamura, S. Jiwajinda, J. Terao, and H. Ohigashi Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the {alpha},{beta}-unsaturated carbonyl group is a prerequisite Carcinogenesis, May 1, 2002; 23(5): 795 - 802. [Abstract] [Full Text] [PDF]

				C. Rodriguez-Burford, M. N. Barnes, D. K. Oelschlager, R. B. Myers, L. I. Talley, E. E. Partridge, and W. E. Grizzle Effects of Nonsteroidal Anti-Inflammatory Agents (NSAIDs) on Ovarian Carcinoma Cell Lines: Preclinical Evaluation of NSAIDs as Chemopreventive Agents Clin. Cancer Res., January 1, 2002; 8(1): 202 - 209. [Abstract] [Full Text] [PDF]