title: Kuguaglycoside C, a constituent of Momordica charantia, induces caspase-independent cell death of neuroblastoma cells.
abstract: Kuguaglycoside C is a triterpene glycoside isolated from the leaves of Momordica charantia, and the biological effects of this compound remain almost unknown. We investigated the anti-cancer effect of kuguaglycoside C against human neuroblastoma IMR-32 cells. In the MTT assay, kuguaglycoside C induced significant cytotoxicity against the IMR-32 cells (IC(50) : 12.6 μM) after 48 h treatment. Although examination by Hoechst 33342 staining revealed that kuguaglycoside C induced nuclear shrinkage at a high concentration (100 μM), no apoptotic bodies were observed on flow cytometry. No activation of caspase-3 or caspase-9 was observed at the effective concentration (30 μM) of kuguaglycoside C. On the other hand, the substance significantly decreased the expression of survivin and cleaved poly (ADP-ribose) polymerase (PARP). Kuguaglycoside C also significantly increased the expression and cleavage of apoptosis-inducing factor (AIF). Moreover, kuguaglycoside C was found to induce caspase-independent DNA cleavage in the dual-fluorescence apoptosis detection assay. These results suggest that kuguaglycoside C induces caspase-independent cell death, and is involved, at least in part, in the mechanism underlying cell necroptosis.
authors.affiliation: Laboratory of Clinical Medicine, School of Pharmacy, Nihon University, Funabashi-shi, Chiba, Japan. tabata.keiichi@nihon-u.ac.jp
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tabata
authors.forename: Aoi
authors.initials: A
authors.lastname: Hamano
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akihisa
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D016923:Cell Death; D053837:DNA Cleavage; D005434:Flow Cytometry; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D029777:Momordica charantia / Q000737:chemistry*; D009447:Neuroblastoma; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006027:Glycosides; D012503:Saponins; C578463:kuguaglycoside C; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9