Combinatorial effect of curcumin and tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) in induction of apoptosis via inhibition of nuclear factor kappa activity and enhancement of caspase-3 activity in chronic myeloid cells: An In-vitro study.

Abstract

Nuclear factor kappa B (NFkB-light-chain-enhancer of activated B-cells) expression and its regulation is a key role in the development of number of malignancies, as NFkB mediates the balance between cell death and its survival. Therefore, NFkB regulation constitutes an attractive target to overcome the resistance to chemotherapeutic agents in anticancer therapy. Curcumin, as a chemopreventive agent, has a potential role in inhibiting cell growth in a variety of malignancies. Thus, this study was aimed to investigate the efficacy of curcumin along with tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) in KCL-22 myeloid cells along with an investigation of the mechanism by which both the agents exert their effects. KCL-22 cells were exposed to different doses of curcumin and TRAIL alone and in combination. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, caspase activity by fluorescent method, protein expression by western Blot, and NFkB activity by electrophoretic mobility shift assays, respectively. Cell viability assay revealed that when both the agents, curcumin and TRAIL, were used together, there was reduced cell viability in dose- and time-dependent manner as compared to each agent alone. Curcumin and TRAIL enhanced the caspase-3 activity as compared to caspase-8 and caspase-9. Both the agents induced apoptosis in KCL-22 cells by suppressing the IκB kinase and NFkB activity. Our results conclude that curcumin and TRAIL effectively induce the apoptosis through the inhibition of NFkB activity and by enhancing the caspase-3 activity. Thus, curcumin may prove as a potent inhibitor of NFkB by representing its role in cancer pathogenesis, especially in chronic myeloid leukemia cells.