College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China.
School of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Apr;397(4):2437-2445. doi: 10.1007/s00210-023-02770-5. Epub 2023 Oct 17.
Hepatocellular carcinoma (HCC) has high morbidity and mortality, and effective therapies are lacking. Gallic acid (GA), a natural phenolic compound derived from plants, has been reported to prevent the onset and progression of various cancers. However, there is limited elaboration on the potential mechanisms and anticancer effects of GA on hepatocellular carcinoma. Inducing ferroptosis of tumor cells has become one of the most promising ways to eradicate tumor cells. However, the effect of GA on HCC ferroptosis remains unknown. We evaluated the impact of GA on cell viability, migration, and mitochondrial morphology in HepG2 cells. Our study identified a critical role of GA in inducing ferroptosis in HepG2 cells. Mechanistically, we found that GA could inhibit the expression of a ferroptosis-related protein SLC7A11 and GPX4 in HepG2, by blocking β-catenin transport from nuclear to the cytoplasm, thus inducing the inactivation of the Wnt/β-catenin pathway. Our study has confirmed that GA is a novel ferroptosis inducer of HC, suggesting GA could be a promising candidate for the clinical treatment of HCC.
肝细胞癌（HCC）发病率和死亡率高，缺乏有效的治疗方法。没食子酸（GA）是一种从植物中提取的天然酚类化合物，已被报道可预防多种癌症的发生和发展。然而，GA 对肝癌的潜在机制和抗癌作用的阐述有限。诱导肿瘤细胞发生铁死亡已成为消除肿瘤细胞最有前途的方法之一。然而，GA 对 HCC 铁死亡的影响尚不清楚。我们评估了 GA 对 HepG2 细胞活力、迁移和线粒体形态的影响。我们的研究确定了 GA 在诱导 HepG2 细胞铁死亡中的关键作用。在机制上，我们发现 GA 可以通过阻断β-连环蛋白从核到细胞质的转运来抑制铁死亡相关蛋白 SLC7A11 和 GPX4 在 HepG2 中的表达，从而诱导 Wnt/β-连环蛋白通路失活。我们的研究证实 GA 是 HCC 的一种新型铁死亡诱导剂，提示 GA 可能是 HCC 临床治疗的有前途的候选药物。
