管腔 A 型乳腺癌治疗的新策略:vulpinic 酸作为抗肿瘤剂可诱导铁死亡和细胞凋亡机制。
A new therapeutic strategy for luminal A-breast cancer treatment: vulpinic acid as an anti-neoplastic agent induces ferroptosis and apoptosis mechanisms.
发表日期:2024 Aug 19
作者:
Ayşe Hale Alkan, Mine Ensoy, Demet Cansaran-Duman
来源:
Cellular & Molecular Immunology
摘要:
乳腺癌是女性常见的浸润性肿瘤,最常见的乳腺癌亚型是Luminal A。激素疗法是Luminal A的主要治疗方法,但治疗选择有限。 Vulpinic Acid (VA) 是一种地衣化合物,可抑制癌细胞。在这里,我们的目的是揭示VA在管腔A型乳腺癌中的功能作用和机制。进行了与铁死亡机制相关的实验,以揭示胡平酸对管腔 A 型乳腺癌的作用及其潜在机制。结果表明,VA 通过降低 MCF-7 细胞中谷胱甘肽 (GSH) 水平,同时增加脂质活性氧 (ROS)、脂质过氧化 (MDA) 和细胞内 Fe2+ 水平来诱导铁死亡途径。用VA处理MCF-7细胞后,铁死亡相关基因表达谱显着改变。 Western blot分析显示,VA处理后GPX4蛋白水平下调,LPCAT3蛋白水平上调。我们的研究表明细胞凋亡和铁死亡在 VA 介导的 MCF-7 乳腺癌细胞肿瘤抑制中共同作用。这些发现表明,VA(一种抗肿瘤药物)有可能通过铁死亡途径治疗 luminal A 靶向乳腺癌。© 2024。作者获得 Springer Science Business Media, LLC(Springer Nature 旗下子公司)的独家许可。
Breast cancer is a common invasive tumor in women, and the most common subtype of breast cancer is luminal A. Hormonal therapies are the primary treatment for luminal A, but treatment options are limited. Vulpinic acid (VA), a lichen compound, inhibited cancer cells. Here, we aimed to reveal the functional role and mechanism of VA in luminal A breast cancer. Experiments associated with the ferroptosis mechanism were performed to reveal the role of vulpinic acid on luminal A-breast cancer and the underlying mechanisms. The results showed that VA induced the ferroptosis pathway by decreasing glutathione (GSH) levels while increasing lipid reactive oxygen species (ROS), lipid peroxidation (MDA), and intracellular Fe2+ levels in MCF-7 cells. After treatment of MCF-7 cells with VA, the ferroptosis-related gene expression profile was significantly altered. Western blot analysis showed that GPX4 protein levels were down-regulated and LPCAT3 protein levels were up-regulated after VA treatment. Our study suggests that apoptosis and ferroptosis act together in VA-mediated tumor suppression in MCF-7 breast cancer cells. These findings suggest that VA, an anti-neoplastic agent, could potentially treat luminal A targeted breast cancer via the ferroptosis pathway.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.