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. 2023 Jun 1;18(4):381-391.
doi: 10.4103/1735-5362.378085. eCollection 2023 Jul-Aug.

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

Bahareh Samii  1 , Abbas Jafarian  1   2 , Mohamad Rabbani  1   2 , Behzad Zolfaghari  3 , Soheila Rahgozar  4 , Elnaz Pouraboutaleb  4
Affiliations

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

Bahareh Samii et al. Res Pharm Sci. .

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 IC50), 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 μg/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 μg/mL in CCRF-CEM/R and tragacanthin at 50 and 100 μg/mL in CCRF-CEM/MTX and at 2-100 μg/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.

Keywords: ALL; APS; Bassorin; MDR1 gene; Tragacanthin.

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Conflict of interest statement

The authors declared no conflicts of interest in this study.

Figures

Fig. 1
Fig. 1
Determination of the IC50 of methotrexate in CCRF-CEM. Data are presented as mean ± SEM, n = 3.
Fig. 2
Fig. 2
The effects of APS on the viability of CCRF-CEM cells. CCRF-CEM cells were treated with APS alone, CCRF-CEM/MTX cells received APS in combination with MTX at 0.1 μM, and CCRF-CEM/R cells were treated with APS in combination with MTX at 0.6 μM. Results are shown as mean ± SEM of 3 experiments. *P < 0.05 Indicates significant differences compared to the respective negative control group (cells that did not receive any treatments). CCRF-CEM and CCERF-CEM/R cells treated with MTX at 0.1 and 0.6 μM, respectively were considered positive controls. APS, Astragalus polysaccharides; MTX, methotrexate.
Fig. 3
Fig. 3
The effects of bassorin on the viability of CCRF-CEM cells. CCRF-CEM cells were treated with bassorin alone, CCRF-CEM/MTX cells received bassorin in combination with MTX at 0.1, and CCRF-CEM/R cells were treated with bassorin in combination with MTX at 0.6 μM. Results are shown as mean ± SEM, n = 3. *P < 0.05 Indicates significant differences compared to negative control groups (cells that did not receive any treatments) and ■P < 0.05 vs positive control groups (CCRF-CEM and CCERF-CeM/R cells treated with MTX at 0.1 and 0.6 μM, respectively). APS, Astragalus polysaccharides; MTX, methotrexate.
Fig. 4
Fig. 4
The effects of tragacanthin on the viability of CCRF-CEM cells. CCRF-CEM cells were treated with tragacanthin alone, CCRF-CEM/MTX cells received tragacanthin in combination with MTX at 0.1, and CCRF-CEM/R cells were treated with tragacanthin in combination with MTX at 0.6 μM. Results are shown as mean ± SEM, n = 3. *P < 0.05 Indicates significant differences compared to negative control groups (cells that did not receive any treatments) and ■P < 0.05 vs positive control groups (CCRF-CEM and CCERF-CEM/R cells treated with MTX at 0.1 and 0.6 μM, respectively). APS, Astragalus polysaccharides; MTX, methotrexate.
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