Kuguaglycoside C, a constituent of Momordica charantia, induces caspase-independent cell death of neuroblastoma cells

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 (IC50: 12.6 mu M) after 48h treatment. Although examination by Hoechst 33342 staining revealed that kuguaglycoside C induced nuclear shrinkage at a high concentration (100 mu M), no apoptotic bodies were observed on flow cytometry. No activation of caspase-3 or caspase-9 was observed at the effective concentration (30 mu M) 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. (Cancer Sci 2012; 103: 2153-2158)