柑橘源薯蓣皂苷对黑色素瘤的作用:通过抑制PI3K/Akt/mTOR通路诱导细胞凋亡和自噬。

IF 2.6 4区 医学 Q3 CHEMISTRY, MEDICINAL
Jie Li, Mingyuan Xu, Nanhui Wu, Fei Wu, Jiashe Chen, Xiaoxiang Xu, Fei Tan, Yeqiang Liu
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引用次数: 0

摘要

背景:薯蓣皂苷(Diosmetin, DIOS)是一种天然丰富的类黄酮,具有多种生物活性,有望作为抗癌药物。然而,DIOS对皮肤黑色素瘤的抗癌作用及其机制尚不清楚。目的:探讨DIOS在皮肤黑色素瘤中的抗肿瘤作用及其机制。方法:采用多种体外和体内实验,结合RNA测序(RNA-seq),确定DIOS潜在的抗皮肤黑色素瘤能力和机制。结果:DIOS显著抑制细胞增殖并诱发细胞凋亡,且呈剂量和时间依赖性。同时,DIOS显著提高了促凋亡蛋白(Cleaved caspase-3、Bax、Cleaved PARP、Cleaved caspase-9)的表达,下调了Bcl-2的表达。此外,DIOS显著上调LC3B-II和Atg5蛋白的表达,下调p62蛋白的表达。值得注意的是,自噬抑制剂预处理可显著抑制dioos诱导的细胞凋亡和自噬。在机制上,通过western blot分析和RNA-seq鉴定DIOS抑制PI3K/Akt/mTOR信号通路。最后,采用同基因小鼠模型进行的体内实验证实了DIOS的抗肿瘤作用,其表现出高水平的细胞凋亡和自噬。结论:这些研究结果表明,DIOS作为一种潜在的黑色素瘤治疗药物,通过抑制PI3K/Akt/mTOR通路引发细胞凋亡和自噬,发挥其抗肿瘤作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effects of Citrus-derived Diosmetin on Melanoma: Induction of Apoptosis and Autophagy Mediated by PI3K/Akt/mTOR Pathway Inhibition.

Background: Diosmetin (DIOS) is a naturally abundant flavonoid and possesses various biological activities that hold promise as an anti-cancer agent. However, the anti-cancer activities and underlying mechanism of DIOS on cutaneous melanoma remain unclear.

Objective: This study seeks to explore the anti-tumor effect and mechanism of DIOS in cutaneous melanoma.

Methods: Here, a variety of in vitro and in vivo experiments, combined with RNA sequencing (RNA-seq), were employed to ascertain the potential anti-cutaneous melanoma capacity and mechanism of DIOS.

Results: The results demonstrated that DIOS considerably impeded cell proliferation and triggered cell apoptosis in a dose- and time-dependent manner. Concurrently, DIOS markedly elevated the expression of pro-apoptotic proteins (Cleaved caspase-3, Bax, Cleaved PARP, and Cleaved caspase-9) and downregulated the expression of Bcl-2. Additionally, DIOS markedly upregulated the protein expressions of LC3B-II and Atg5, while downregulating p62 protein expression. Notably, pre-treatment with an autophagy inhibitor significantly inhibited DIOSinduced cell apoptosis and autophagy. Mechanistically, DIOS was identified to repress the PI3K/Akt/mTOR signaling pathway by western blot analyses and RNA-seq. Finally, in vivo experiments using a syngeneic mouse model confirmed the anti-tumor effect of DIOS, which exhibited high levels of apoptosis and autophagy.

Conclusion: These findings propose that DIOS acts as a potential melanoma therapy that exerts its anti-tumor effects by triggering apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathway.

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来源期刊
Anti-cancer agents in medicinal chemistry
Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL
CiteScore
5.10
自引率
3.60%
发文量
323
审稿时长
4-8 weeks
期刊介绍: Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.
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