一种海洋生物小分子通过促进内质网应激诱导的细胞凋亡和自噬抑制前列腺癌的生长

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Mao Ding, Mu He, Dan Li, Shuaishuai Ding, Chenjia Dong, Hongchao Zhao, Huajie Song, Kui Hong, Hengcheng Zhu
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引用次数: 0

摘要

MHO7(6-epi-ophiobolin G)是从红树林真菌中提取的一种新型成分,对乳腺癌有显著的抗癌作用。然而,MHO7 对前列腺癌(PCa)抗癌作用的确切机制尚未完全阐明。因此,本研究旨在评估 MHO7 对 PCa 细胞的作用,并阐明其潜在机制。研究人员进行了一系列体外实验,包括细胞计数试剂盒-8、平板克隆形成试验、流式细胞术分析、电子显微镜、免疫荧光染色、Western 印迹和分子动力学模拟。此外,我们还采用了体内肿瘤异种移植模型。我们的研究结果表明,MHO7在低浓度(2 μM)时可诱导细胞自噬,在相对高浓度(4 μM和8 μM)时可诱导细胞凋亡,从而显著抑制PCa细胞的生长。此外,MHO7 还会引发内质网(ER)应激,进而通过 IRE1α/XBP-1s 信号通路激活细胞自噬和凋亡。值得注意的是,IRE1α的敲除明显减少了MHO7诱导的自噬和细胞凋亡。此外,MHO7靶向IRE1α蛋白,从而增强了其稳定性。在肿瘤异种移植模型中,MHO7也表现出了很强的抗癌活性。我们的研究表明,MHO7在不同浓度下都能激活ER应激诱导的自噬和细胞凋亡,并通过上调IRE1α的表达来促进自噬和细胞凋亡,因此具有作为PCa抗癌剂的巨大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Marine-Derived Small Molecule Inhibits Prostate Cancer Growth by Promoting Endoplasmic Reticulum Stress Induced Apoptosis and Autophagy.

MHO7 (6-epi-ophiobolin G), a novel component extracted from a mangrove fungus, exhibits significant anticancer effects against breast cancer. However, the precise mechanism underlying the anticancer effects of MHO7 in prostate cancer (PCa) is yet to be fully elucidated. Therefore, this study was undertaken to assess the effect of MHO7 on PCa cells and elucidate its underlying mechanism. A series of in vitro experiments were conducted, including Cell Counting Kit-8, and plate clone formation assays, flow cytometry analysis, electron microscopy, immunofluorescence staining, western blotting, and molecular dynamics simulation. Additionally, in vivo tumor xenograft models were employed. Our findings revealed that MHO7 could induce cellular autophagy at low concentration (2 μM) and apoptosis at relatively high concentration (4 and 8 μM), leading to significant PCa cell growth inhibition. Furthermore, MHO7 triggered endoplasmic reticulum (ER) stress, which subsequently stimulated autophagy and apoptosis via IRE1α/XBP-1s signaling pathway activation. Notably, IRE1α knockdown markedly reduced MHO7-induced autophagy and apoptosis. Moreover, MHO7 targeted the IRE1α protein, thereby enhancing its stability. MHO7 also exhibited substantial anticancer activity in tumor xenograft models. Our study revealed that MHO7 holds considerable potential as an anticancer agent against PCa, attributable to its activation of ER stress-induced autophagy and apoptosis at different concentrations, facilitated by the upregulation of IRE1α expression.

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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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