Eclalbasaponin II induces autophagic and apoptotic cell death in human ovarian cancer cells

Autor: Yoon Jin Cho, Jeong-Hwa Woo, Jae-Seung Lee, Dae Sik Jang, Kyung-Tae Lee, Jung-Hye Choi
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Journal of Pharmacological Sciences, Vol 132, Iss 1, Pp 6-14 (2016)
Druh dokumentu: article
ISSN: 1347-8613
DOI: 10.1016/j.jphs.2016.02.006
Popis: 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 G1 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.
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