Autophagy is a catabolic process for degradation of intracellular components and plays an important role in the development and growth of cancer. Our preliminary screening confirmed that an extract from the root of Saussurea lappa remarkably suppressed the proliferation of HepG2 hepatocellular carcinoma cells and inhibited autophagy. In this study, we explored the effects of costunolide (CL) and dehydrocostuslactone (DCL), which are bioactive sesquiterpene lactones in this extract, on autophagy modulation in HepG2 cells. An analysis of autophagy-related proteins demonstrated that CL and DCL blocks the autophagy process that leads to the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 (p62). LC3 turnover assays indicated that CL and DCL trigger autophagy inhibition by blocking the autophagic flux, thereby resulting in the accumulation of LC3-II and p62. These results are encouraging and warrant further study of CL and DCL for potential use as autophagy inhibiting agents for liver cancer therapy.

自噬是细胞内组分降解的分解代谢过程，在癌症的发生和发展中起重要作用。我们的初步筛选证实了雪莲的根提取物显着抑制HepG2肝癌细胞的增殖并抑制自噬。在这项研究中，我们探讨了提取物中具有生物活性倍半萜烯内酯的木香酚内酯（CL）和脱氢木糖内酯（DCL）对HepG2细胞中自噬调节的影响。对自噬相关蛋白的分析表明，CL和DCL阻断了自噬过程，导致了微管相关蛋白1轻链3（LC3）和SQSTM1 / p62（p62）的积累。LC3周转分析表明，CL和DCL通过阻断自噬通量来触发自噬抑制作用，从而导致LC3-II和p62的积累。这些结果令人鼓舞，并且有必要进一步研究CL和DCL作为肝癌治疗中自噬抑制剂的潜在用途。