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.
Cui
Yanhong
Y
Chemical Engineering College, Zhengzhou University, No. 100 Science Road, Zhengzhou, 450001, People's Republic of China.
Lu
Zhongbing
Z
Bai
Lin
L
Shi
Zhenhua
Z
Zhao
Wen-En
WE
Zhao
Baolu
B
D000813:Anilides / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D047495:PPAR gamma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D019207:beta Carotene / Q000494:pharmacology*
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D016588:Anticarcinogenic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047495:PPAR gamma; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019207:beta Carotene; D051546:Cyclooxygenase 2; D005978:Glutathione