Open AccessKuguaglycoside C , a constituent of M omordica charantia , induces caspase‐independent cell death of neuroblastoma cells
Author(s) -
Tabata Keiichi,
Hamano Aoi,
Akihisa Toshihiro,
Suzuki Takashi
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12021
Subject(s) - neuroblastoma , apoptosis , chemistry , biology , biochemistry , cell culture , genetics
Kuguaglycoside C is a triterpene glycoside isolated from the leaves of M omordica 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 H oechst 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.