title: The novel p53-dependent metastatic and apoptotic pathway induced by vitexin in human oral cancer OC2 cells.
abstract: Vitexin, identified as apigenin-8-C-D-glucopyranoside, a natural flavonoid compound found in certain herbs such as hawthorn herb, has been reported to exhibit anti-oxidative, anti-inflammatory, anti-metastatic and antitumor properties. The aim of this study was to investigate the possible existence of p53-dependent pathway underlying vitexin-induced metastasis and apoptosis in human oral cancer cells, OC2 cells. Vitexin decreased cell viability significantly. Meanwhile, the expression of tumor suppressor p53 and a small group of its downstream genes, p21(WAF1) and Bax, were upregulated. The p53 inhibitor pifithrin-α (PFT-α) knockdown of the signaling of p53 led vitexin to lose its antitumor effect and inhibited the expression of p53 downstream genes, p2(WAF1) and Bax. Vitexin had anti-metastatic potential accompanied with increasing plasminogen activator inhibitor 1 (PAI-1) accumulation and decreasing matrix metalloproteinase-2 expression. Our present study evidenced, by using p53 inhibitor PFT-α, PAI-1 and peroxisome proliferator-activated receptor γ are downstream genes of p53 in vitexin-induced signaling. MAPK inhibitor PD98059 decreased the OC2 cells viability significantly. The expression of p53 and its downstream genes p21(WAF1) and Bax were enhanced by blocking the activation of p42/p44 MAPK in response to treatment with vitexin. Moreover, p42/p44 MAPK played a negative role in p53-dependent metastasis and apoptosis. We give evidence for the first time that the novel p53-dependent metastatic and apoptotic pathway induced by vitexin in human oral cancer OC2 cells.
authors.affiliation: School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shih-Huang
authors.initials: SH
authors.lastname: Yang
authors.forename: Pao-Hsin
authors.initials: PH
authors.lastname: Liao
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Pan
authors.forename: Shiow-Ling
authors.initials: SL
authors.lastname: Chen
authors.forename: Shih-Shen
authors.initials: SS
authors.lastname: Chou
authors.forename: Ming-Yung
authors.initials: MY
authors.lastname: Chou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D052160:Benzothiazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D047495:PPAR gamma / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D052160:Benzothiazoles; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005419:Flavonoids; D047495:PPAR gamma; D017395:Plasminogen Activator Inhibitor 1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D014050:Toluene; D047310:Apigenin; C032731:vitexin; C121565:pifithrin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one