Effects of cotreatment of 12-O-tetradecanoylphorbol-13-acetate and H2O2 on apoptotic regulation via AMP-activated protein kinase-cyclooxygenase-2 signals.
Colorectal cancer displays elevated cyclooxygenase-2 (COX-2) expression, and several studies have suggested that COX-2 expression is associated with parameters of aggressive colon cancer. AMP-activated protein kinase (AMPK) is a sensor of cellular energy status, and recent studies indicate that AMPK activation strongly suppresses cell proliferation in nonmalignant cells as well as in tumor cells. As a metabolic sensing signal, AMPK is involved in cancer cell apoptosis. In HT-29 colon cancer cells, the regulation of COX-2 expression by treating with TPA (12-O-tetradecanoylphorbol-13-acetate), low-level H(2)O(2), high-level H(2)O(2), and finally the combinations of TPA and low H(2)O(2) or high H(2)O(2) was investigated. We found that COX-2 expression levels with treatment reacted as follows: with TPA alone > TPA and low H(2)O(2) > low H(2)O(2) > high H(2)O(2) > TPA and high H(2)O(2). COX-2 regulation by these agents was accompanied by the alteration of AMPK control. The apoptotic bodies were detected as follows: high level of H(2)O(2) > TPA > low level of H(2)O(2). The present findings suggest that both COX-2 stimulators (TPA and H(2)O(2)) might have differential effects on COX-2 and AMPK regulation and further apoptotic regulation.
Lee
Yun-Kyoung
YK
Department of Food and Nutrition, Hannam University Daedeok Valley Campus, Daejeon, Korea.
Lee
Mee-Sook
MS
Kim
Young-Min
YM
Park
Ock Jin
OJ
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D016877:Oxidants / Q000494:pharmacology; D012265:Ribonucleotides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D016877:Oxidants; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D006861:Hydrogen Peroxide; D051546:Cyclooxygenase 2; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D013755:Tetradecanoylphorbol Acetate