title: Eclalbasaponin II induces autophagic and apoptotic cell death in human ovarian cancer cells.
abstract: 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 G1population. 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.
authors.affiliation: 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.
authors.forename: Yoon Jin
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: 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.
authors.forename: Jeong-Hwa
authors.initials: JH
authors.lastname: Woo
authors.affiliation: 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.
authors.forename: Jae-Seung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Jang
authors.affiliation: Department of Life & Nanopharmaceutical Science, Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.affiliation: 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. Electronic address: jchoi@khu.ac.kr.
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Choi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D012503:Saponins; C580755:eclalbasaponin I; C000618671:eclalbasaponin II; D009828:Oleanolic Acid; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C022999:echinocystic acid
keywords: Apoptosis; Autophagy; Eclalbasaponin II; Ovarian cancer