Chen Luyao, Guo Yaping, Wu Zixuan, Zhao Shuwu, Zhang Zhaiyi, Zheng Fang, Sun Likang, Hao Zheng, Xu Chen, Wang Tao, Peng Yanfei
School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Acta Biochim Biophys Sin (Shanghai). 2021 Dec 8;53(12):1662-1669. doi: 10.1093/abbs/gmab144.
Lipid metabolism disorder caused by the upregulation of lipogenic genes is a typical feature of prostate cancer. The synthesis of fatty acids is enhanced to accelerate the development of prostate cancer and is considered as a potential therapeutic target. Epicatechin gallate, an active compound of green tea, has been reported to modulate lipid metabolism. In this research, the potential role of epicatechin gallate in prostate cancer cells was evaluated. The results indicated that epicatechin gallate downregulates the expression of acetyl-CoA carboxylase, ATP citrate lyase, and fatty acid synthase in prostate cancer cells and prostate xenograft tissues, suggesting that epicatechin gallate can inhibit de novo fatty acid synthesis. Moreover, epicatechin gallate significantly restrains the migration rather than the viability of prostate cancer cells. PI3K/AKT/mTOR signaling pathway, which exhibits regulatory effect on lipogenesis, is also inhibited under epicatechin gallate treatment, while pretreatment with AKT activator SC79 or mTOR activator MHY1485 blocks the inhibitory effect of epicatechin gallate on the expression of lipogenic genes and the migration of prostate cancer cells. In conclusion, this study revealed that epicatechin gallate impairs the synthesis of fatty acids via inhibition PI3K/AKT/mTOR signaling pathway and then attenuates the migration of prostate cancer cells.
由生脂基因上调引起的脂质代谢紊乱是前列腺癌的典型特征。脂肪酸合成增强会加速前列腺癌的发展，并被视为一个潜在的治疗靶点。表没食子儿茶素没食子酸酯是绿茶的一种活性化合物，据报道它可调节脂质代谢。在本研究中，对表没食子儿茶素没食子酸酯在前列腺癌细胞中的潜在作用进行了评估。结果表明，表没食子儿茶素没食子酸酯可下调前列腺癌细胞和前列腺异种移植组织中乙酰辅酶A羧化酶、ATP柠檬酸裂解酶和脂肪酸合酶的表达，这表明表没食子儿茶素没食子酸酯可抑制脂肪酸的从头合成。此外，表没食子儿茶素没食子酸酯显著抑制前列腺癌细胞的迁移而非活力。对脂肪生成具有调节作用的PI3K/AKT/mTOR信号通路在表没食子儿茶素没食子酸酯处理下也受到抑制，而用AKT激活剂SC79或mTOR激活剂MHY1485预处理可阻断表没食子儿茶素没食子酸酯对生脂基因表达和前列腺癌细胞迁移的抑制作用。总之，本研究表明表没食子儿茶素没食子酸酯通过抑制PI3K/AKT/mTOR信号通路损害脂肪酸合成，进而减弱前列腺癌细胞的迁移。
