Hederagenin suppresses ovarian cancer via targeting mitochondrial fission through dynamin-related protein 1.
Hederagenin suppresses ovarian cancer via targeting mitochondrial fission through dynamin-related protein 1.
复制标题
DOI：
10.1016/j.ejphar.2023.176188
复制
发表时间：
2023-11
影响因子：
5
通讯作者：
Fang Su;Xin Sui;Jiabao Xu;Q. Liu;Junfeng Li;Wenhong Liu;Ye Xu;Zhiqian Zhang;Fangfang Tao-Fa
中科院分区：
文献类型：
--
作者：
Fang Su;Xin Sui;Jiabao Xu;Q. Liu;Junfeng Li;Wenhong Liu;Ye Xu;Zhiqian Zhang;Fangfang Tao-Fa
常春藤素是从植物常春藤中分离出来的三萜类化合物，被发现在体内和体外具有抗癌、抗炎、抗抑郁和抗纤维化特性。在本研究中，研究了卵巢癌（OC）中线粒体分裂与常春藤素诱导的细胞凋亡之间的关系，并阐明了其潜在机制。使用集落形成和 CCK-8 测定分析常春藤素对 OC 细胞的细胞毒性。常春藤素对OC细胞的作用也通过小鼠异种移植肿瘤模型得到了验证。进行流式细胞术分析来检查常春藤素对线粒体膜电位、细胞凋亡和细胞周期 OC 细胞的影响。 MitoTracker Red（CMXRos）染色观察线粒体形态。通过Western blot检测Bak、Bcl-2、Caspase 3、Caspase 9、Cyclin D1和Bax的蛋白水平。本研究发现常春藤素可以有效地抑制体内和体外SKOV3和A2780细胞的增殖。此外，常春藤素还可以改变线粒体膜电位，诱导 OC 细胞 S 期和 G0/G1 期阻滞、线粒体形态变化和细胞凋亡。此外，我们的研究结果进一步表明，常春藤素通过抑制动力相关蛋白 1 (Drp1)（一种重要的线粒体分裂因子）来改变线粒体形态。此外，Drp1过表达可以逆转常春藤素诱导的细胞凋亡，而Drp1敲低则具有相反的效果。此外，常春藤素可能会触发 OC 细胞中的 BAX 线粒体易位和细胞凋亡。这些结果为常春藤素调节线粒体形态与抑制卵巢癌之间的关系提供了新的视角。
A triterpenoid isolated from the plantHedera helix, hederagenin was discovered to have anti-cancer, anti-inflammatory, anti-depressant and anti-fibrosis properties bothin vivoandin vitro. In this study, the relationship between mitochondrial fission and hederagenin-induced apoptosis in ovarian cancer (OC) was investigated and the underlying mechanisms were deciphered. Hederagenin's cytotoxicity on OC cells was analyzed using colony formation and CCK-8 assays. The effect of hederagenin on OC cells was also verified by a mouse xenograft tumor model. Flow cytometric analysis was conducted to examine hederagenin's effects on mitochondrial membrane potential, apoptosis, and cell cycle OC cells. MitoTracker Red (CMXRos) staining was performed to observe the mitochondrial morphology. The protein levels of Bak, Bcl-2, Caspase 3, Caspase 9, Cyclin D1 and Bax were measured by Western blot. This study found that hederagenin could suppress thein vivoandin vitroSKOV3 and A2780 cell proliferation in an effective manner. Besides, hederagenin altered the mitochondrial membrane potential, induced S-phase and G0/G1-phase arrest, mitochondrial morphology changes, and apoptosis in OC cells. Additionally, our findings further demonstrated that hederagenin changed the mitochondrial morphology by suppressing dynamin-related protein 1 (Drp1), a crucial mitochondrial division factor. Moreover, Drp1 overexpression could reverse hederagenin-induced apoptosis, whereas the Drp1 knockdown had the opposite effect. Furthermore, hederagenin may trigger BAX mitochondrial translocation and apoptosis in OC cells. These results provided a novel perspective on the relationship between the modulation of mitochondrial morphology and the suppression of ovarian cancer by hederagenin.