Inhibition of cyclooxygenase-1 lowers proliferation and induces macroautophagy in colon cancer cells.
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 G(0)/G(1)-phase cell cycle arrest. The anti-proliferative effect was associated with down-regulation of c-Fos, cyclin E(2) and E(2)F-1 and up-regulation of p21(Waf1/Cip1) and p27(Kip1). 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.
Wu
William Ka Kei
WK
Institute of Digestive Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. wukakei@cuhk.edu.hk
Sung
Joseph Jao Yiu
JJ
Wu
Ya Chun
YC
Li
Hai To
HT
Yu
Le
L
Li
Zhi Jie
ZJ
Cho
Chi Hin
CH
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D014617:Vacuoles / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D011720:Pyrazoles; C115461:SC 560; C025946:3-methyladenine; D051545:Cyclooxygenase 1; D000225:Adenine