Effects of Phenolic Acid on Body Fat, Fatty Liver and Bladder Cancer

• Main Authors: Chung-Chia Liao, 廖重佳
• Other Authors: 王朝鐘
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/64001795466210134686

博士 === 中山醫學大學 === 生化暨生物科技研究所 === 104 === Caffeic acid (CA) can inhibit toxin-induced liver injury. In this study, CA is assessed for its lipid lowering potential when oleic acid is used to induce non-alcoholic fatty liver disease in human HepG2 cells. The results showed that both the triglyceride and cholesterol content are decreased in the HepG2 cells by using the enzymatic colorimetric method. CA enhances the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream target enzyme, acetyl-CoA carboxylase. CA down-regulates the lipogenesis gene expression of sterol regulatory element-binding protein-1 and its target genes through AMPK activation. C57BL/6 mice were fed a normal diet or a HFD (20% fat) with or without caffeic acid for 6 weeks. The supplementation of caffeic acid significantly lowered body weight, visceral fat mass, plasma GOT and GPT levels, FAS activity, and free fatty acid compared to the HFD group. Caffeic acid also lowered triglyceride and cholesterol concentrations in plasma and liver. Gallic acid (GA) has been shown to inhibit carcinogenesis in animal models and various cancer cell lines. The TSGH-8301 bladder cancer cell line was treated with different concentrations of gallic acid. It showed that GA inhibited TSGH-8301 bladder cancer cell proliferation via the PI3K/Akt and MAPK/ERK pathway. Our results showed that GA decreased Skp2 protein level and attenuated Skp2-p27 association. It is suggested that gallic acid acts upstream of the proteasome to control p27 levels and ultimately inhibits G2/M phase transition. Our study showed that GA suppressed bladder cancer cell invasion and migration through RhoB/p-AKT/p-IkB/NF-kB/MMP-2 signaling pathway. GA also increased ER alpha expression, which prevented bladder cancer in animal study. GA decreased FAS protein level in our study. It is possible that gallic acid inhibited TSGH-8301 bladder cancer cell growth, invasion and migration through inhibition of fatty acid synthase.