Anti-tumor effect of M2000 (β-d-mannuronic acid) on the expression of inflammatory molecules in the prostate cancer cell

Abstract

Aim: The importance of chronic inflammation during the progression of prostate cancer (PCa) is well-known. M2000 (β-d-mannuronic acid) is a novel anti-inflammatory drug. According to its potential capacity for the inhibition of molecules involved in creating conditions of inflammation, it is reasonable to assess the anti-inflammatory role of M2000 in PCa cells. Methods: MTT assay was performed to determine the cytotoxicity of M2000 in PC3 cells. Correspondingly, these cells were cultured and then treated with low (25 µg/ml) and high (50 µg/ml) doses of M2000 as optimal doses. Thereafter, real-time RT-PCR, flow cytometry analysis, and zymography were performed to evaluate the expressions of MYD-88, NF-kB, IL-8, COX-2, MMP-2, and MMP-9 molecules. Results: Of note, the M2000 at the concentration of ≤200 μg/ml had no cytotoxicity effect on the cells. MYD-88 gene expression was significantly down-regulated at both low and high doses in the M2000-treated cells compared to the control (p = .017 and p = .001, respectively). The expression of the NF-kB was also reduced at both the gene and protein levels (all p values were <.001). The expression of IL-8 and COX-2 genes was also down-regulated in the high dose of M2000 (p<.001, p = .001, respectively). The decreased expression of the MMP-9 gene was observed at both doses (both p values were <.001). Conclusion: Inhibitory effects of M2000 on the activity of MMPs in the LPS/M2000-treated cells were evident, but not in the M2000-treated cells. M2000 as a new anti-inflammatory drug appears to constitute a potential agent for down-regulation of inflammatory molecules in the PCa cells.