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.
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.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Seungyeon
authors.initials: S
authors.lastname: Hyun
authors.forename: Man Sub
authors.initials: MS
authors.lastname: Kim
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Song
authors.forename: Yesol
authors.initials: Y
authors.lastname: Bak
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Ham
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Lee
authors.forename: Jintae
authors.initials: J
authors.lastname: Hong
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
chemical_list: C542058:4-O-methylhonokiol; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D017705:Lignans; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9