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Inhibition of cyclooxygenase-1 lowers proliferation and induces macroautophagy in colon cancer cells |
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| Authors: | William Ka Kei Wu Joseph Jao Yiu Sung Ya Chun Wu Le Yu Zhi Jie Li |
| Institution: | a Institute of Digestive Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong b Department of Medicine & Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong c Department of Pharmacology, 4/F, Basic Medical Sciences Building, The Chinese University of Hong Kong, Shatin, NT, Hong Kong |
| Abstract: | Evolving evidence supports that cyclooxygenase-1 (COX-1) takes part in colon carcinogenesis. The effects of COX-1 inhibition on colon cancer cells, however, remains obscured. In this study, we demonstrate that COX-1 inhibitor sc-560 inhibited colon cancer cell proliferation with concomitant G0/G1-phase cell cycle arrest. The anti-proliferative effect was associated with down-regulation of c-Fos, cyclin E2 and E2F-1 and up-regulation of p21Waf1/Cip1 and p27Kip1. In addition, sc-560 induced macroautophagy, an emerging mechanism of tumor suppression, as evidenced by the formation of LC3+ autophagic vacuoles, enhanced LC3 processing, and the accumulation of acidic vesicular organelles and autolysosomes. In this connection, 3-methyladenine, a Class III phosphoinositide 3-kinase inhibitor, significantly abolished the formation of LC3+ autophagic vacuoles and the processing of LC3 induced by sc-560. To conclude, this study reveals the unreported relationship between COX-1 and proliferation/macroautophagy of colon cancer cells. |
| Keywords: | Cyclooxygenase-1 Colon cancer Proliferation Cell cycle Macroautophagy |
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