title: Kudsuphilactone B, a nortriterpenoid isolated from Schisandra chinensis fruit, induces caspase-dependent apoptosis in human ovarian cancer A2780 cells.
abstract: A phytochemical study on the fruits of Schisandra chinensis led to the isolation and characterization of nineteen compounds. The structures of the isolates were determined to be schizandrin, deoxyschizandrin, angeloylgomisin H, gomisin A, gomisin J, (-)-gomisin L1, (-)-gomisin L2, wuweizisu C, gomisin N, meso-dihydroguaiaretic acid, kadsuphilactone B, α-ylangenol, α-ylangenyl acetate, β-chamigrenal, β-chamigrenic acid, 4-hydroxybenzoic acid, protocatechuic acid, p-methylcarvacrol, and indole-3-acetic acid. Of these, some lignans and a nortriterpene showed cytotoxic activity in human ovarian and endometrial cancer cells. In particular, a nortriterpenoid kadsuphilactone B exhibited significant cytotoxic activity with IC50values below 25 μM in both A2780 and Ishikawa cells. Kadsuphilactone B induced apoptotic cell death and stimulated the activation of caspase-3, -8, and -9 and the cleavages of poly (ADP-ribose) polymerase. Caspase inhibitors attenuated the pro-apoptotic activity of kudsuphilactone B. In addition, kadsuphilactone B altered the expression levels of B cell lymphoma 2 (Bcl-2) family proteins. Moreover, activation of MAPKs was modulated by kadsuphilactone B in a dose-dependent manner. Taken together, these results show that kadsuphilactone B induces caspase-dependent apoptosis in human cancer cells via the regulation of Bcl-2 family protein and MAPK signaling.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Miran
authors.initials: M
authors.lastname: Jeong
authors.affiliation: Department of Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Hye Mi
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Oriental Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea. jchoi@khu.ac.kr.
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea. dsjang@khu.ac.kr.|Department of Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea. dsjang@khu.ac.kr.
authors.forename: Dae Sik
authors.initials: DS
authors.lastname: Jang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D032141:Schisandra / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; C000620497:kudsuphilactone B; D020169:Caspases
keywords: Apoptosis; Cancer; Caspase; Kadsuphilactone B; Nortriterpenoid; Schisandra chinensis