<br>Kuwanon C 通过靶向线粒体和内质网抑制肿瘤细胞增殖并诱导细胞凋亡,International Journal of Molecular Sciences

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Kuwanon C 通过靶向线粒体和内质网抑制肿瘤细胞增殖并诱导细胞凋亡
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2024-07-30 , DOI: 10.3390/ijms25158293
Gangxiang Yuan ₁ , Peng Qian ₁ , Lin Chen ₁ , Ningjia He ₁

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Kuwanon C 是桑树家族中发现的一种独特的黄酮类化合物，其特征是两个异戊烯基。虽然之前的研究主要集中在桑酮 C 的各种特性上，例如抗氧化、降血糖、抗菌、食品保存、皮肤美白和延长线虫寿命，但很少有人关注它在肿瘤疾病中的潜在作用。在本研究中，我们研究了桑酮C对宫颈癌细胞的抗肿瘤作用，并阐明了其具体的作用机制。我们使用各种实验技术评估了 kuwanon C 的抗肿瘤作用，包括细胞增殖测定、伤口愈合测定、EdU 488 增殖测定、线粒体膜电位测定、ROS 水平测定、细胞周期、细胞凋亡分析以及 kuwanon C 靶位点的研究和分子对接。结果显示，kuwanon C 显着影响 HeLa 细胞的细胞周期进程，破坏其线粒体膜电位，并诱导细胞内 ROS 水平大幅增加。此外，kuwanon C对HeLa细胞表现出显着的抗增殖和促凋亡作用，超越了紫杉醇和顺铂等常用抗肿瘤药物的性能。值得注意的是，与紫杉醇相比，kuwanon C 表现出卓越的功效，同时也更容易获得。我们的研究表明，kuwanon C 通过与线粒体和内质网膜相互作用发挥有效的抗肿瘤作用，诱导 ROS 的大量产生，破坏其正常结构，抑制细胞周期进程，并刺激细胞凋亡信号通路，最终导致细胞死亡。海拉肿瘤细胞。作为一种源自桑树的异戊烯基化合物，桑农 C 有望成为开发有效抗肿瘤药物的潜在候选者。

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Kuwanon C Inhibits Tumor Cell Proliferation and Induces Apoptosis by Targeting Mitochondria and Endoplasmic Reticulum

Kuwanon C is a unique flavonoid found in the mulberry family, characterized by two isopentenyl groups. While previous research has focused on various properties of kuwanon C, such as antioxidant, hypoglycemic, antimicrobial, food preservation, skin whitening, and nematode lifespan extension, little attention has been given to its potential role in oncological diseases. In this study, we investigate the antitumor effect of kuwanon C in cervical cancer cells and elucidate its specific mechanism of action. We assessed the antitumor effects of kuwanon C using various experimental techniques, including cell proliferation assay, wound healing assays, EdU 488 proliferation assay, mitochondrial membrane potential assay, ROS level assay, cell cycle, apoptosis analysis, and studies on kuwanon C target sites and molecular docking. The results revealed that kuwanon C significantly impacted the cell cycle progression of HeLa cells, disrupted their mitochondrial membrane potential, and induced a substantial increase in intracellular ROS levels. Moreover, kuwanon C exhibited notable anti-proliferative and pro-apoptotic effects on HeLa cells, surpassing the performance of commonly used antitumor drugs such as paclitaxel and cisplatin. Notably, kuwanon C demonstrated superior efficacy while also being more easily accessible compared to paclitaxel. Our study demonstrates that kuwanon C exerts potent antitumor effects by its interaction with the mitochondrial and endoplasmic reticulum membranes, induces a significant production of ROS, disrupts their normal structure, inhibits cell cycle progression, and stimulates apoptotic signaling pathways, ultimately resulting in the death of HeLa tumor cells. As an isopentenyl compound derived from Morus alba, kuwanon C holds great promise as a potential candidate for the development of effective antitumor drugs.

更新日期：2024-07-31

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