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        Stigmast-4-en-6β-ol-3-one decreases viability and induces apoptosis and ferroptosis in liver cancer cells by reducing E2F1

        Zhiyun Zhang,Jian Wang,Weiping Wan,Zhengchao Shen,Aixue Zuo,Rong Chen,Qinyi Wu,Enli Cai,Feng Huang,Rongping Zhang,Xinan Shi 한국통합생물학회 2023 Animal cells and systems Vol.27 No.1

        Hepatocellular carcinoma (HCC) is a frequently occurring malignant gastrointestinal cancer. The 5-year survival rate of HCC is still below 8%, and thus, identifying more effective therapeutic methodsis needed. Here, we evaluated the effects of Stigmast-4-en-6β-ol-3-one (S463) on the viability andcolony formation of liver cancer cells. S463 treatment decreased the viability and inducedapoptosis and ferroptosis in liver cancer cells, and also increased cellular malondialdehyde(MDA) and lipid peroxidation levels. In S463 treated cells, the expression level of Bax wasincreased, and the expression level of GPX4 was reduced, and the cleavage of PARP wasimproved. We also found that S463 treatment downregulated E2F1 and upregulated p53 atboth the mRNA and protein levels. Importantly, rescue experiments revealed thatoverexpression of E2F1 partially restored S463-induced Bax and p53 upregulation and GPX4downregulation and counteracted the S463-induced decrease in cell viability and colonyformation and the S463-induced increase in MDA and lipid peroxidation levels. Our findingssuggest that S463 significantly inhibits viability and colony formation and induces apoptosisand ferroptosis in liver cancer cells via E2F1.

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