Mechanisms of curcumin-induced apoptosis of Ehrlich's ascites carcinoma cells

Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn ), is a potent antioxidant and anti-inflammatory agent. It has been recentl y demonstrated to possess discrete chemopreventive activities. However, the molecular mechanisms underlying such anticancer properties of curcumin sti ll remain unrealized, although it has been postulated that induction of apo ptosis in cancer cells might be a probable explanation. In the current stud y, curcumin was found to decrease the Ehrlich's ascites carcinoma (EAC) cel l number by the induction of apoptosis in the tumor cells as evident from f low-cytometric analysis of cell cycle phase distribution of nuclear DNA and oligonucleosomal fragmentation. Probing further into the molecular signals leading to apoptosis of EAC cells, we observed that curcumin is causing tu mor cell death by the up-regulation of the proto-oncoprotein Bax, release o f cytochrome c from the mitochondria, and activation of caspase-3. The stat us of Bcl-2 remains unchanged in EAC, which would signify that curcumin is bypassing the Bcl-2 checkpoint and overriding its protective effect on apop tosis. (C) 2001 Academic Press.