Effects of Cotreatment of 12-O-tetradecanoylphorbol-13-acetate and H2O2 on Apoptotic Regulation via AMP-Activated Protein KinaseCyclooxygenase-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 H2O2, high-level H2O2, and finally the combinations of TPA and low H2O2 or high H2O2 was investigated. We found that COX-2 expression levels with treatment reacted as follows: with TPA alone > TPA and low H2O2 > low H2O2 > high H2O2 > TPA and high H2O2. COX-2 regulation by these agents was accompanied by the alteration of AMPK control. The apoptotic bodies were detected as follows: high level of H2O2 > TPA > low level of H2O2. The present findings suggest that both COX-2 stimulators (TPA and H2O2) might have differential effects on COX-2 and AMPK regulation and further apoptotic regulation.
cox-2 ampk apoptosis tpa low-level h2o2 high-level h2o2