2015 ; 25(3):
|Author||Seungyeon Hyun, Man Sub Kim, Yong Seok Song, Yesol Bak, Sun Young Ham, Dong Hun Lee, Jintae Hong, Do Young Yoon|
|Affiliation||Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea|
|Title||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|
J. Microbiol. Biotechnol.2015 ; 25(3):
|Abstract||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 (PPARγ) activation, followed by inhibition
of the PI3K/Akt pathway and intrinsic pathway induction. MH upregulated PPARγ and PTEN
expression levels while it decreased p-Akt in the MH-induced apoptotic process, thereby
supporting the fact that MH is a PPARγ 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 PPARγ/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.|
|Keywords||4-O-methylhonokiol, cervical cancer, PPARγ agonist, apoptosis|
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