The effect of vitexin on apoptosis and adipogenesis

• Main Authors: Shih-Huang Yang, 楊世煌
• Other Authors: Ming-Yung Chou
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/14154660782849298050

博士 === 中山醫學大學 === 牙醫學系博士班 === 102 === 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 signaling pathways underlying vitexin-induced apoptosis and anti-adipogenesis. 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 knockdown the signaling of p53 led vitexin lost its anti-tumor effect and inhibited the expression of p53 downstream genes, p21WAF1 and Bax. Vitexin had anti-metastatic potential accompanied with increasing plasminogen activator inhibitor 1 (PAI-1 ) accumulation and decreasing matrix metalloproteinase-2 (MMP-2) expression. Our present study evidenced, by using p53 inhibitor pifithrin-α, PAI-1 and PPARγ 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 ERK 1/2 MAPK in response to treatment with vitexin. Moreover, ERK 1/2 MAPK played a negative role in p53-dependent metastasis and apoptosis. Vitexin inhibited adipose accumulation, glucose consumption and triglyceride synthesis. The expression of ERK 1/2 MAPK greatly induced, whereas the expression of adipogenic markers Akt and peroxisome proliferator-activated receptor γ (PPARγ) diminished. ERK 1/2 MAPK inhibitor PD98059 (10 μM) significantly enhanced lipid accumulation, triglyceride synthesis and the expression of adipogenic markers. However, PD98059 had no effect on glucose consumption. In regulation of glycolysis, vitexin induced the expression of glycerol-3-phosphate dehydrogenase (GPDH) at higher dosage (50 and 100 μM) and without any effect on glucose-6-phosphate dehydrogenase (G6PDH) expression. PD98059 had an opposing effect that it significantly increased the expression of G6PDH, but decreased the expression of GPDH. Vitexin increased the lactic acid synthesis to about 3.8 folds in concentration dependent, whereas, PD98059 decreased the level of lactic acid in media to about 72% when compared with controls. Moreover, PD98059 abolished the anti-adipogenic effect of vitexin. Vitexin influence the expansion of adipose tissue through its ability to inhibit preadipocyte migration to about 80% via decreased the activity of active MMP-2. We demonstrated evidences for the first time thathe novel p53-dependent metastatic and apoptotic pathway induced by vitexin in human oral cancer OC2 cells and using of vitexin to against adipose accumulation. Moreover, blockade pentose phosphate pathway may be a novel strategy for obesity prevention and therapy.