Estrogen receptor‐α36 is involved in diallyl sulfide‐induced inhibition of malignant growth of HepG2 and Huh7 hepatocellular carcinoma cells

作者：Weiqi Wu, Hongfei Chen, Ruobing Wang, Jiaming Chen, Haiyan Yu, Zhixuan Wei, Xiaotian Liu, Mingru Xue, Qiongxia Chen, Hongyan Zhou, Zhengqi Fu · 发表于：Environmental Toxicology · 年份：2021 · DOI：10.1002/tox.23396 · 被引用次数：18 · 研究领域：Garlic and Onion Studies、Fungal Plant Pathogen Control、Chemotherapy-induced organ toxicity mitigation

Hepatocellular carcinoma (HCC) is a highly malignant disease that currently lacks effective treatment. Epidemiological studies have suggested the preventive role of raw garlic intake in different tumors, such as HCC. Although diallyl sulfide (DAS), the main component of garlic extracts, has been reported to inhibit the growth of HCC cells, the underlying mechanism remains elusive. This study aimed to investigate the inhibitory effect of DAS on the growth of HepG2 and Huh7 hepatocellular carcinoma cells and its underlying mechanism. HepG2 and Huh7 cells were treated with DAS and nude mice were intrahepatically injected with human HCC HepG2 cells and maintained with or without DAS administration for 28 days. MTS and clonogenic assays revealed that DAS inhibited the growth and clonogenicity of HepG2 and Huh7 hepatocellular carcinoma cells. Furthermore, DAS inhibited the growth of xenograft tumors accompanied by a decreased rate of pathological karyomitosis as observed by H&E staining. The expression levels of estrogen receptor-α36 (ER-α36) and epidermal growth factor receptor (EGFR) in HepG2 and Huh7 cells and in xenograft tumors derived from HepG2 cells after DAS treatment were detected by immunohistochemistry and western blotting. We found that DAS disrupted the positive regulatory loop between ER-α36 and EGFR, and decreased the phosphorylation of AKT at Ser 473 both in vivo and in vitro. DAS also induced cell apoptosis, as evidenced by Hoechst and TUNEL staining. Western blot...