title: 4-O-methylhonokiol inhibits colon tumor growth via p21-mediated suppression of NF-κB activity.
abstract: Biphenolic components in the Magnolia family have shown several pharmacological activities such as antitumor effects. This study investigated the effects of 4-O-methylhonokiol (MH), a constituent of Magnolia officinalis, on human colon cancer cell growth and its action mechanism. 4-O-methylhonokiol (0-30 μM) decreased constitutive activated nuclear factor (NF)-κB DNA binding activity and inhibited growth of human colon (SW620 and HCT116) cancer cells. It also caused G₀-G₁ phase cell cycle arrest followed by an induction of apoptotic cell death. However, knockdown with small interfering RNA (siRNA) of p21 or transfection with cyclin D1/Cdk4 binding site-mutated p21 abrogated MH-induced cell growth inhibition, inhibition of NF-κB activity as well as expression of cyclin D1 and Cdk4. Conversely, inhibition of NF-κB with specific inhibitor or siRNA augmented MH-induced apoptotic cell death. 4-O-methylhonokiol inhibited tumor growth, NF-κB activity and expression of antiapoptotic proteins; however, it increased the expression of apoptotic proteins as well as p21 in xenograft nude mice bearing SW620 cancer cells. The present study reveals that MH causes p21-mediated human colon cancer cell growth inhibition through suppression of NF-κB and indicates that this compound by itself or in combination with other anticancer agents could be useful for the treatment of cancer.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Ju Hoon
authors.initials: JH
authors.lastname: Oh
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Ban
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Cho
authors.forename: Miran
authors.initials: M
authors.lastname: Jo
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Byeongwoo
authors.initials: B
authors.lastname: Ahn
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000037:antagonists & inhibitors
chemical_list: C542058:4-O-methylhonokiol; D001713:Biphenyl Compounds; C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017705:Lignans; D016328:NF-kappa B; D010936:Plant Extracts; D034741:RNA, Small Interfering; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4