beta-Carotene induces apoptosis and up-regulates peroxisome proliferator-activated receptor gamma expression and reactive oxygen species production in MCF-7 cancer cells

Although the pharmacological role of beta-carotene in the prevention and treatment of many Cancer cells has received increasing attention, the molecular mechanisms underlying such chemopreventive activity are not clear. Since Peroxisome Proliferator-activated Receptor gamma (PPAR-gamma) has been implicated in regulating breast Cancer cell differentiation and Apoptosis, the effects of beta-carotene on the PPAR-gamma-mediated pathway and its association with Reactive Oxygen Species production in MCF-7 cells were investigated in the present study. The results demonstrated that beta-carotene significantly increased PPAR-gamma mRNA and protein levels in time-dependent manner. In addition, beta-carotene increased the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) expression and decreased the prostanoid synthesis rate-limiting Enzyme cyclooxygenase-2 expression. 2-chloro-5-nitro-N-phenylbenzamide (GW9662), an irreversible PPAR-gamma antagonist, partly attenuated the cell death caused by beta-carotene. Further, Reactive Oxygen Species (ROS) production was induced by beta-carotene, resulting in mitochondrial dysfunction and cytochrome C release. Reduced glutathione (GSH) treatment decreases the intracellular ROS and prevents cytochrome C release and cell Apoptosis induced by beta-carotene. In total, these observations suggest that the synergistic effect of PPAR-gamma expression and ROS production may account for beta-carotene-mediated Anticancer activities.