Simvastatin in combination with bergamottin potentiates TNF-induced apoptosis through modulation of NF-κB signalling pathway in human chronic myelogenous leukaemia

AbstractContext Simvastatin (SV) and bergamottin (BGM) are known to exhibit diverse anti-cancer and anti-inflammatory activities.Objective Very little is known about the potential efficacy of combination of these two agents to potentiate TNF-induced apoptosis in human chronic myelogenous leukaemia (CML).Materials and methods In the present study, we investigated whether SV combined with BGM mediates its effect through suppression of NF-κB-signalling pathway.Results We found that the combination treatment enhanced cytotoxicity and potentiated the apoptosis induced by TNF as indicated by intracellular esterase activity, Annexin V staining and caspase activation. This effect of co-treatment correlated with down-regulation of various gene products that mediate cell proliferation (cyclin D1), cell survival (cIAP-1, Bcl-2, Bcl-xL and Survivin), invasion (MMP-9) and angiogenesis (VEGF); all known to be regulated by NF-κB. SV combined with BGM also produced TNF-induced cell-cycle arrest in S-phase and this arrest...