Effects of cotreatment of 12-O-tetradecanoylphorbol-13-acetate and H2O2 on apoptotic regulation via AMP-activated protein kinase-cyclooxygenase-2 signals

Abstract

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.