Abstract：
A triterpenoid isolated from the plant Hedera helix, hederagenin was discovered to have anti-cancer, anti-inflammatory, anti-depressant and anti-fibrosis properties both in vivo and in 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 the in vivo and in vitro SKOV3 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.
摘要：
从植物Hedera螺旋中分离出的三萜类化合物，hederagenin被发现有抗癌作用,抗炎,在体内和体外的抗抑郁和抗纤维化特性。在这项研究中,研究了线粒体裂变与hederagenin诱导的卵巢癌（OC）凋亡之间的关系，并解释了其潜在机制。使用集落形成和CCK-8测定分析了Hederagenin对OC细胞的细胞毒性。hederagenin对OC细胞的作用也通过小鼠异种移植肿瘤模型得到证实。进行流式细胞术分析以检查hederagenin对线粒体膜电位的影响,凋亡，和细胞周期OC细胞。进行MitoTracker红(CMXRos)染色以观察线粒体形态。Bak的蛋白质水平,Westernblot检测Bcl-2、Caspase3、Caspase9、CyclinD1和Bax。本研究发现hederagenin可以有效抑制体内和体外SKOV3和A2780细胞的增殖。此外,hederagenin改变了线粒体膜电位,诱导S相和G0/G1相阻滞，线粒体形态变化，OC细胞凋亡。此外,我们的发现进一步证明，hederagenin通过抑制dynamin相关蛋白1（Drp1）改变线粒体形态，一个至关重要的线粒体分裂因子.此外，Drp1过表达可以逆转hederagenin诱导的细胞凋亡，而Drp1敲除具有相反的效果。此外，hederagenin可能引发OC细胞BAX线粒体易位和凋亡。这些结果为线粒体形态的调节与hederagenin抑制卵巢癌之间的关系提供了新的视角。
