Induction of G2/M arrest and inhibition of cyclooxygenase-2 activity by curcumin in human bladder cancer T24 cells

Abstract

Curcumin, a polyphenol compound derived from Curcuma longa Linn, has been recognized as a promising anti-cancer drug due to its multiple properties including anti-inflammatory, anti-oxidant and anti-carcinogenic activities. To elucidate the mechanisms by which curcumin inhibits human bladder carcinoma T24 cell proliferation, we tested the effects of curcumin on specific cell cycle pathways and on the expression of cyclooxygenases (COXs). Curcumin inhibited the growth of T24 cells and induced G2/M arrest in a concentration-dependent manner, effects associated with the down-regulation of cyclin A and up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1). However, other G2/M regulatory molecules, such as cyclin A, Cdc2, Cdk2, Wee1 and Cdc25C, were not modulated by curcumin treatment. Furthermore, curcumin decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which correlated with a decrease in prostaglandin E2 (PGE2) synthesis. These observations suggest that curcumin may have therapeutic potential for bladder cancer patients.