The effects of Astragalus polysaccharides, tragacanthin, and bassorin on methotrexate-resistant acute lymphoblastic leukemia

Abstract

BACKGROUND AND PURPOSE: One strategy to overcome methotrexate (MTX) resistance in acute lymphoblastic leukemia is suppressing MDR1 expression. It has been proved Astragalus polysaccharides (APS) exert their anticancer effect by reversing drug resistance. Due to the structural similarity of tragacanthin and bassorin with APS, we aimed to investigate the effects of the aforementioned polysaccharides on the expression of the MDR1 gene in the MTX-treated CCRF-CEM cells. EXPERIMENTAL APPROACH: Cytotoxicity of APS, bassorin, and tragacanthin on CCRF-CEM, CCRF-CEM/MTX (cells treated with MTX at IC(50)), and CCRF-CEM/R cells (CCRF-CEM cells resistant to MTX) was evaluated by MTT assay. The effect of all three compounds on MDR1 expression was evaluated using RT-PCR. FINDINGS/RESULTS: All the concentrations of tragacanthin, bassorin, and APS (except at 0.8-100 mug/mL in CCRF-CEM) decreased the viability of all the cells compared to the negative control group; and against the positive control (MTX-treated cells), only bassorin at 20-100 mug/mL in CCRF-CEM/R and tragacanthin at 50 and 100 mug/mL in CCRF-CEM/MTX and at 2-100 mug/mL in CCRF-CEM/R decreased cell viability. Tragacanthin diminished MDR1 expression in CCRF-CEM/MTX and CCRF-CEM/R cells, which MTX had already induced. CONCLUSION AND IMPLICATION: According to the results of this study, tragacanthin was a potent cytotoxic agent against CCRF-CEM cells and enhanced the chemosensitivity of CCRF-CEM/MTX and CCRF-CEM/R cells to MTX by down-regulation of MDR1 gene expression. Therefore, it could be a promising compound against cancer. Other possible mechanisms of action of tragacanthin should be evaluated and further in vitro and in vivo investigations are required.