Objective Jatropha curcas has been used in traditional medicine in Africa to treat cancer for thousands of years. This study aimed to examine the anti-endometrial cancer effect of Curcusone C, a naturally occurring rhamnofolane diterpene, isolated from J. curcas and reveal its molecular mechanism of action. Results Curcusone C treatment caused significant anti-proliferative and apoptotic effects in human endometrial cancer (EC) Ishikawa and HEC-1A cells in a dose-dependent manner. Exposure of EC cells to Curcusone C resulted in apoptosis, which was associated with cytochrome c release, caspase-3 and caspase-9 activation, Bcl-xL/Bax dysregulation, and decreased expression of inhibitors of apoptosis proteins, such as XIAP and survivin. The inhibitory effect induced by Curcusone C was greatly impaired by the overexpression of survivin or Bax −/− MEFs or the knockdown of Bim expression. Moreover, Curcusone C activated mitogen-activated protein kinases, and the ERK inhibitor U0126 significantly attenuated the growth-inhibitory and apoptotic effects of Curcusone C in Ishikawa cells. Conclusion Taken together, the results demonstrate the anti-endometrial cancer potential of Curcusone C for the treatment of endometrial cancer.

中文翻译：

---

姜黄素 C 通过线粒体依赖性凋亡和 ERK 通路诱导子宫内膜癌细胞凋亡

目的麻疯树在非洲的传统医学中用于治疗癌症已有数千年的历史。本研究旨在检测从麻疯树中分离出来的天然鼠李树素二萜 Curcusone C 的抗子宫内膜癌作用，并揭示其分子作用机制。结果 Curcusone C 治疗在人子宫内膜癌 (EC) Ishikawa 和 HEC-1A 细胞中以剂量依赖性方式引起显着的抗增殖和凋亡作用。EC 细胞暴露于 Curcusone C 导致细胞凋亡，这与细胞色素 c 释放、caspase-3 和 caspase-9 激活、Bcl-xL/Bax 失调以及凋亡蛋白抑制剂（如 XIAP 和存活蛋白）的表达降低有关。由 Survivin 或 Bax -/- MEF 的过度表达或 Bim 表达的敲低大大削弱了由 Curcusone C 诱导的抑制作用。此外，Curcusone C 激活丝裂原活化蛋白激酶，ERK 抑制剂 U0126 显着减弱 Curcusone C 在 Ishikawa 细胞中的生长抑制和凋亡作用。结论 综上所述，结果证明了姜黄素 C 治疗子宫内膜癌的抗子宫内膜癌潜力。