Additive antitumour effect of D-allose in combination with cisplatin in non-small cell lung cancer cells

Abstract

D-allose is a rare sugar which has been shown to have growth inhibitory effects in several kinds of malignancies. However, the effect of D-allose on lung cancer progression has not been previously studied. To investigate the antitumour effect of D-allose in lung cancer cells and its mechanism, human non-small cell lung cancer (NSCLC) cell lines (squamous cell carcinomas: EBC1 and VMRC-LCD; adenocarcinomas: A549, HI1017, RERF-LC-A1 and NCI-H1975) were treated with D-allose (50 mM) with or without cisplatin (5 μM). D-allose inhibited cell growth, particularly in EBC1 and VMRC-LCD cells. In combination with cisplatin, D-allose had a synergistic growth inhibitory effect. D-allose increased the expression of thioredoxin interacting protein (TXNIP) at mRNA and protein levels. D-allose decreased the proportion of cells in G1 phase and increased those in S and G2/M phases. For in vivo experiments, EBC1 cells were inoculated into BALB/C-NU mice. After tumourigenesis, D-allose and cisplatin were injected. In this mouse xenograft model, additional treatment with D-allose showed a significantly greater tumour inhibitory effect compared with cisplatin alone, accompanied by lower Ki-67 and higher TXNIP expression. In conclusion, D-allose inhibited NSCLC cell proliferation in vitro and tumour progression in vivo. In combination with cisplatin, D-allose had an additional antitumour effect. Specifically, increased TXNIP expression and subsequent G2/M arrest play a role in D-allose-mediated antitumour effects in NSCLC.