Autophagy is a catabolic process that degrades dysfunctional proteins and organelles and plays critical roles in cancer development. Our preliminary screening identified that extracts of the fruits of Arctium lappa and the fruits of Forsythia suspensa notably suppressed the proliferation of hepatocellular carcinoma HepG2 cells and downregulated the autophagy. In this study, we explored the effect of arctigenin (ARG), a bioactive lignan in both extracts, on cell proliferation and autophagy-related proteins in HepG2 cells. ARG inhibited the proliferation of HepG2 cells. Analysis of autophagy-related proteins demonstrated that ARG might block the autophagy that leads to sequestosome 1/p62 (p62) accumulation. The stage of inhibition in autophagy by ARG differed from those by the autophagy inhibitors 3-methyladenine (3-MA) or chloroquine (CQ). ARG could also inhibit starvation-induced autophagy. Further analysis of apoptosis-related proteins indicated that ARG did not affect caspase-3 activation and PARP cleavage, suggesting that the antiproliferative effect of ARG can occur independently of apoptosis. In summary, our study showed that ARG suppresses cell proliferation and inhibits autophagy, and might lead to the development of agents for autophagy research and cancer chemoprevention.

中文翻译：

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Arctigenin通过抑制肝细胞癌细胞中的自噬来抑制细胞增殖。

自噬是一种分解代谢过程，可降解功能障碍的蛋白质和细胞器，并在癌症发展中发挥关键作用。我们的初步筛选确定了牛Arc子和连翘的果实提取物显着抑制肝细胞癌HepG2细胞的增殖并下调自噬。在这项研究中，我们探索了两种提取物中具有生物活性的木脂素arctogenin（ARG）对HepG2细胞中细胞增殖和自噬相关蛋白的影响。ARG抑制HepG2细胞的增殖。自噬相关蛋白的分析表明，ARG可能会阻断自噬，导致自体脂质体1 / p62（p62）积累。ARG抑制自噬的阶段与自噬抑制剂3-甲基腺嘌呤（3-MA）或氯喹（CQ）的抑制阶段不同。ARG还可以抑制饥饿引起的自噬。对凋亡相关蛋白的进一步分析表明，ARG不会影响caspase-3激活和PARP裂解，提示ARG的抗增殖作用可以独立于细胞凋亡而发生。总之，我们的研究表明ARG抑制细胞增殖并抑制自噬，并可能导致自噬研究和癌症化学预防药物的开发。