Yang Nian, Li Chen, Li Hongliang, Liu Ming, Cai Xiaojun, Cao Fengjun, Feng Yibin, Li Minglun, Wang Xuanbin
Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital, Hubei University of Medicine, Shiyan, China.
Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Biomedical Research Institute, Hubei University of Medicine, Shiyan, China.
Front Pharmacol. 2019 Jun 25;10:709. doi: 10.3389/fphar.2019.00709. eCollection 2019.
(Thunb.) Moldenke (He Shou Wu) has been used for about 20 centuries as a Chinese medicinal herb for its activities of anticancer, anti-hyperlipidemia, and anti-aging. Previously, we found that He Shou Wu ethanol extract could induce apoptosis in hepatocellular carcinoma cells, and we also screened its active components. In this study, we investigated whether lowering lipid metabolism of emodin, a main active component in He Shou Wu, was associated with inhibitory effects in hepatocellular carcinoma cells. The correlation of apoptosis induction and lipid metabolism was investigated. The intrinsic apoptotic cell death, lipid production, and their signaling pathways were investigated in emodin-treated human hepatocellular carcinoma cells Bel-7402. The data showed that emodin triggered apoptosis in Bel-7402 cells. The mitochondrial membrane potential (ΔΨm) was reduced in emodin-treated Bel-7402 cells. We also found that emodin activated the expression of intrinsic apoptosis signaling pathway-related proteins, cleaved-caspase 9 and 3, Apaf 1, cytochrome c (CYTC), apoptosis-inducing factor, endonuclease G, Bax, and Bcl-2. Furthermore, the level of triglycerides and desaturation of fatty acids was reduced in Bel-7402 cells when exposed to emodin. Furthermore, the expression level of messenger RNA (mRNA) and protein of sterol regulatory element binding protein 1 (SREBP1) as well as its downstream signaling pathway and the synthesis and the desaturation of fatty acid metabolism-associated proteins (adenosine triphosphate citrate lyase, acetyl-CoA carboxylase alpha, fatty acid synthase (FASN), and stearoyl-CoA desaturase D) were also decreased. Notably, knock-out of in Bel-7402 cells was also found to induce less intrinsic apoptosis than did emodin. In conclusion, these results indicated that emodin could induce apoptosis in an SREBP1-dependent and SREBP1-independent manner in hepatocellular carcinoma cells.
（蓼科）何首乌（Polygonum multiflorum (Thunb.) Moldenke）作为一种中药材，因其具有抗癌、抗高血脂和抗衰老的活性，已被使用了约20个世纪。此前，我们发现何首乌乙醇提取物可诱导肝癌细胞凋亡，并且我们还筛选了其活性成分。在本研究中，我们调查了何首乌中的主要活性成分大黄素降低脂质代谢是否与对肝癌细胞的抑制作用有关。研究了凋亡诱导与脂质代谢的相关性。在大黄素处理的人肝癌细胞Bel-7402中，研究了内源性凋亡性细胞死亡、脂质生成及其信号通路。数据表明，大黄素可触发Bel-7402细胞凋亡。大黄素处理的Bel-7402细胞中线粒体膜电位（ΔΨm）降低。我们还发现大黄素可激活内源性凋亡信号通路相关蛋白的表达，包括切割的半胱天冬酶9和3、凋亡蛋白酶激活因子1、细胞色素c（CYTC）、凋亡诱导因子、核酸内切酶G、Bax和Bcl-2。此外，当Bel-7402细胞暴露于大黄素时，甘油三酯水平和脂肪酸去饱和度降低。此外，固醇调节元件结合蛋白1（SREBP1）的信使核糖核酸（mRNA）和蛋白表达水平及其下游信号通路以及脂肪酸代谢相关蛋白（柠檬酸-ATP裂解酶、乙酰辅酶A羧化酶α、脂肪酸合酶（FASN）和硬脂酰辅酶A去饱和酶D）的合成和去饱和度也降低。值得注意的是，在Bel-7402细胞中敲除[此处原文缺失具体基因名称]也发现比大黄素诱导的内源性凋亡更少。总之，这些结果表明大黄素可在肝癌细胞中以依赖SREBP1和不依赖SREBP1的方式诱导凋亡。
