KMID : 0545120150250030334
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Journal of Microbiology and Biotechnology 2015 Volume.25 No. 3 p.334 ~ p.342
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Peroxisome Proliferator-Activated Receptor-Gamma Agonist 4-O-Methylhonokiol Induces Apoptosis by Triggering the Intrinsic Apoptosis Pathway and Inhibiting the PI3K/Akt Survival Pathway in SiHa Human Cervical Cancer Cells
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Hyun Seung-Yeon
Kim Man-Sub Song Yong-Seok Bak Ye-Sol Ham Sun-Young Lee Dong-Hun Hong Jin-Tae Yoon Do-Young
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Abstract
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4-O-Methylhonokiol (MH), a bioactive compound derived from Magnolia officinalis, is known to exhibit antitumor effects in various cancer cells. However, the precise mechanism of its anticancer activity in cervical cancer cells has not yet been studied. In this study, we demonstrated that MH induces apoptosis in SiHa cervical cancer cells by enhancing peroxisome proliferator-activated receptor-gamma (PPAR¥ã) activation, followed by inhibition of the PI3K/Akt pathway and intrinsic pathway induction. MH upregulated PPAR¥ã and PTEN expression levels while it decreased p-Akt in the MH-induced apoptotic process, thereby supporting the fact that MH is a PPAR¥ã activator. Additionally, MH decreased the expression of Bcl-2 and Bcl-XL, inducing the intrinsic pathway in MH-treated SiHa cells. Furthermore, MH treatment led to the activation of caspase-3/caspase-9 and proteolytic cleavage of polyADP ribose polymerase. The expression levels of Fas (CD95) and E6/E7 oncogenes were not altered by MH treatment. Taken together, MH activates PPAR¥ã/PTEN expression and induces apoptosis via suppression of the PI3K/Akt pathway and mitochondria-dependent pathways in SiHa cells. These findings suggest that MH has potential for development as a therapeutic agent for human cervical cancer.
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KEYWORD
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4-O-methylhonokiol, cervical cancer, PPAR¥ã agonist, apoptosis
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