麦角甾醇通过抑制 AKT/GSK-3beta/β-catenin 通路来抑制乳腺癌细胞的增殖。
Ergosterol inhibits the proliferation of breast cancer cells by suppressing AKT/GSK-3beta/beta-catenin pathway.
发表日期:2024 Aug 24
作者:
Sunita Nilkhet, Wudtipong Vongthip, Pattawika Lertpatipanpong, Anchalee Prasansuklab, Tewin Tencomnao, Siriporn Chuchawankul, Seung Joon Baek
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
乳腺癌是一种影响全球女性的常见恶性肿瘤,需要有效的治疗策略。这项研究探讨了麦角甾醇(一种在食用蘑菇中发现的生物活性化合物)作为乳腺癌治疗候选物的潜力。用麦角甾醇处理乳腺癌细胞系(MCF-7 和 MDA-MB-231),揭示了其抑制细胞活力、诱导细胞周期停滞和抑制球状体形成的能力。从机制上讲,麦角甾醇通过减弱细胞核中的β-连环蛋白易位,对 Wnt/β-连环蛋白信号通路(癌症进展的关键调节因子)具有显着的抑制作用。这种抑制归因于 AKT/GSK-3β 磷酸化的抑制,导致 β-连环蛋白稳定性和活性降低。此外,麦角甾醇治疗影响蛋白质合成和泛素化,可能有助于其抗癌作用。此外,该研究揭示了麦角甾醇治疗后代谢途径的改变,表明其对癌症发展至关重要的代谢过程的影响。这项研究揭示了麦角甾醇发挥抗肿瘤作用的多方面机制,主要集中在 Wnt/β-连环蛋白途径调节和代谢途径破坏。这些发现为麦角甾醇作为乳腺癌治疗候选药物的潜力提供了宝贵的见解,值得进一步研究和临床应用。© 2024。作者。
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.© 2024. The Author(s).