2-Deoxy-D-glucose and ferulic acid modulates radiation response signaling in non-small cell lung cancer cells.

Previously, we reported the radiosensitizing potential of the combination of 2-deoxy-D-glucose (2DG) and ferulic acid (FA) in NCI-H460 non-small cell lung carcinoma cells in vitro. The present study aims to explore the relevant mechanism of cell death induced by the combination of 2DG and FA along with irradiation in NCI-H460 cells. Incubation of NCI-H460 cells with the combination of 2DG and FA for 24 h before irradiation upregulated the expression of proapoptotic proteins p53 and Bax. Combination of 2DG and FA also increased the levels of p21 and GADD45A in NCI-H460 cells. DNA repair inhibition is expected to be a possible mechanism for the radiosensitization observed, which is evidenced by the downregulation of radiation-induced ataxia-telangiectasia mutated gene expression upon treatment with 2DG and/or FA. Moreover, Western blotting analysis of NF-κB and caspase-3 revealed the involvement of apoptotic signals in the cytotoxicity exhibited by the combination of 2DG and FA. Cell cycle analysis data also showed the increased percentage of Sub-G(0) phase cells upon treatment with the combination of 2DG and FA before irradiation. Taken together, the results of our study clearly suggested that the cell death induced by the combination of 2DG and FA along with irradiation would involve alteration in expression of p53, p21, NF-κB, Bax, and caspase-3, indicating oxidative mechanism in NCI-H460 cells.