Ergosterol inhibits the proliferation of breast cancer cells by suppressing AKT/GSK-3beta/beta-catenin pathway

麦角固醇通过抑制AKT/GSK-3beta/beta-catenin通路抑制乳腺癌细胞增殖

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作者:Sunita Nilkhet, Wudtipong Vongthip, Pattawika Lertpatipanpong, Anchalee Prasansuklab, Tewin Tencomnao, Siriporn Chuchawankul, Seung Joon Baek

Abstract

Breast cancer is a prevalent malignancy affecting women globally, necessitating effective treatment strategies. This study explores the potential of ergosterol, a bioactive compound found in edible mushrooms, as a candidate for breast cancer treatment. Breast cancer cell lines (MCF-7 and MDA-MB-231) were treated with ergosterol, revealing its ability to inhibit cell viability, induce cell cycle arrest, and suppress spheroid formation. Mechanistically, ergosterol demonstrated significant inhibitory effects on the Wnt/beta-catenin signaling pathway, a critical regulator of cancer progression, by attenuating beta-catenin translocation in the nucleus. This suppression was attributed to the inhibition of AKT/GSK-3beta phosphorylation, leading to decreased beta-catenin stability and activity. Additionally, ergosterol treatment impacted protein synthesis and ubiquitination, potentially contributing to its anti-cancer effects. Moreover, the study revealed alterations in metabolic pathways upon ergosterol treatment, indicating its influence on metabolic processes critical for cancer development. This research sheds light on the multifaceted mechanisms through which ergosterol exerts anti-tumor effects, mainly focusing on Wnt/beta-catenin pathway modulation and metabolic pathway disruption. These findings provide valuable insights into the potential of ergosterol as a therapeutic candidate for breast cancer treatment, warranting further investigation and clinical application.

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