Cho Yoon Jin, Woo Jeong-Hwa, Lee Jae-Seung, Jang Dae Sik, Lee Kyung-Tae, Choi Jung-Hye
Department of Life & Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, South Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, South Korea.
Department of Life & Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, South Korea; Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, South Korea.
J Pharmacol Sci. 2016 Sep;132(1):6-14. doi: 10.1016/j.jphs.2016.02.006. Epub 2016 Feb 27.
Triterpenoids echinocystic acid and its glycosides, isolated from several Eclipta prostrata, have been reported to possess various biological activities such as anti-inflammatory, anti-bacterial, and anti-diabetic activity. However, the cytotoxicity of the triterpenoids in human cancer cells and their molecular mechanism of action are poorly understood. In the present study, we found that eclalbasaponin II with one glucose moiety has potent cytotoxicity in three ovarian cancer cells and two endometrial cancer cells compared to an aglycone echinocystic acid and eclalbasaponin I with two glucose moiety. Eclalbasaponin II treatment dose-dependently increased sub G population. Annexin V staining revealed that eclalbasaponin II induced apoptosis in SKOV3 and A2780 ovarian cancer cells. In addition, eclalbasaponin II-induced cell death was associated with characteristics of autophagy; an increase in acidic vesicular organelle content and elevation of the levels of LC3-II. Interestingly, autophagy inhibitor BaF1 suppressed the eclalbasaponin II-induced apoptosis. Moreover, eclalbasaponin II activated JNK and p38 signaling and inhibited the mTOR signaling. We further demonstrated that pre-treatment with a JNK and p38 inhibitor and mTOR activator attenuated the eclalbasaponin II-induced autophagy. This suggests that eclalbasaponin II induces apoptotic and autophagic cell death through the regulation of JNK, p38, and mTOR signaling in human ovarian cancer cells.
从多种鳢肠中分离得到的三萜类化合物刺囊酸及其糖苷，据报道具有多种生物活性，如抗炎、抗菌和抗糖尿病活性。然而，这些三萜类化合物在人类癌细胞中的细胞毒性及其分子作用机制尚不清楚。在本研究中，我们发现与具有两个葡萄糖部分的苷元刺囊酸和 eclalbasaponin I 相比，具有一个葡萄糖部分的 eclalbasaponin II 在三种卵巢癌细胞和两种子宫内膜癌细胞中具有较强的细胞毒性。Eclalbasaponin II 处理呈剂量依赖性增加亚 G 期细胞群体。膜联蛋白 V 染色显示 eclalbasaponin II 诱导 SKOV3 和 A2780 卵巢癌细胞凋亡。此外，eclalbasaponin II 诱导的细胞死亡与自噬特征有关；酸性囊泡细胞器含量增加和 LC3-II 水平升高。有趣的是，自噬抑制剂 BaF1 抑制了 eclalbasaponin II 诱导的凋亡。此外，eclalbasaponin II 激活 JNK 和 p38 信号通路并抑制 mTOR 信号通路。我们进一步证明，用 JNK 和 p38 抑制剂以及 mTOR 激活剂预处理可减弱 eclalbasaponin II 诱导的自噬。这表明 eclalbasaponin II 通过调节人卵巢癌细胞中的 JNK、p38 和 mTOR 信号通路诱导凋亡和自噬性细胞死亡。
