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

Abstract Although the pharmacological role of β -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 γ (PPAR- γ ) has been implicated in regulating breast cancer cell differentiation and apoptosis, the effects of β -carotene on the PPAR- γ -mediated pathway and its association with reactive oxygen species production in MCF-7 cells were investigated in the present study. The results demonstrated that β -carotene significantly increased PPAR- γ mRNA and protein levels in time-dependent manner. In addition, β -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- γ antagonist, partly attenuated the cell death caused by β -carotene. Further, reactive oxygen species (ROS) production was induced by β -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 β -carotene. In total, these observations suggest that the synergistic effect of PPAR- γ expression and ROS production may account for β -carotene-mediated anticancer activities.