Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Cells. 2024 Jul 12;13(14):1186. doi: 10.3390/cells13141186.
Autophagy, an intrinsic catabolic mechanism that eliminates misfolded proteins, dysfunctional organelles, and lipid droplets, plays a vital function in energy balance and cytoplasmic quality control, in addition to maintaining cellular homeostasis. Liver cancer such as hepatocellular carcinoma (HCC) is one of the most common causes of cancer deaths globally and shows resistance to several anticancer drugs. Despite the rising incidence and poor prognosis of malignant HCC, the underlying molecular mechanisms driving this aggressive cancer remain unclear. Several natural compounds, such as phytochemicals of dietary and non-dietary origin, affect hepatocarcinogenesis signaling pathways in vitro and in vivo, which may help prevent and treat HCC cells. Current HCC cells treatments include chemotherapy, radiation, and surgery. However, these standard therapies have substantial side effects, and combination therapy enhances side effects for an acceptable therapeutic benefit. Therefore, there is a need to develop treatment strategies for HCC cells that are more efficacious and have fewer adverse effects. Multiple genetic and epigenetic factors are responsible for the HCC cells to become resistant to standard treatment. Autophagy contributes to maintain cellular homeostasis, which activates autophagy for biosynthesis and mitochondrial regulation and recycling. Therefore, modifying autophagic signaling would present a promising opportunity to identify novel therapies to treat HCC cells resistant to current standard treatments. This comprehensive review illustrates how natural compounds demonstrate their anti-hepatocellular carcinoma function through autophagy.
自噬是一种内在的代谢机制，可消除错误折叠的蛋白质、功能失调的细胞器和脂滴，除了维持细胞内环境平衡外，还在能量平衡和细胞质质量控制中发挥着重要作用。肝癌，如肝细胞癌（HCC），是全球癌症死亡的最常见原因之一，对几种抗癌药物具有耐药性。尽管恶性 HCC 的发病率上升和预后不良，但驱动这种侵袭性癌症的潜在分子机制仍不清楚。一些天然化合物，如膳食和非膳食来源的植物化学物质，在体外和体内影响肝癌发生信号通路，这可能有助于预防和治疗 HCC 细胞。目前 HCC 细胞的治疗方法包括化疗、放疗和手术。然而，这些标准疗法有很大的副作用，联合治疗会增加副作用，以获得可接受的治疗效果。因此，需要开发更有效、副作用更小的 HCC 细胞治疗策略。多种遗传和表观遗传因素导致 HCC 细胞对标准治疗产生耐药性。自噬有助于维持细胞内环境平衡，它通过自噬激活生物合成和线粒体调节和回收。因此，修饰自噬信号将为寻找治疗 HCC 细胞对当前标准治疗耐药的新疗法提供一个有前途的机会。本综述全面说明了天然化合物如何通过自噬发挥其抗肝癌功能。
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