AICAR suppresses cell proliferation and synergizes with decitabine in myelodysplastic syndrome via DNA damage induction.

To investigate the efficacy and safety of the AMPK activator AICAR alone or in combination with decitabine on myelodysplastic syndromes (MDS). p-AMPK (Thr172) expression was lower in MDS samples than in healthy donors. AMPK agonist AICAR inhibited the proliferation of MDS cell lines (SKM1 and MDS-L) (P < 0.05). The results from flow cytometry suggested that AICAR induced G0/G1 phase arrest and apoptosis through inducing DNA damage, as confirmed by immunofluorescence analysis in MDS cell lines. AICAR alone or in combination with decitabine was applied to the two MDS cell lines, and the combination index values at all concentrations were significantly < 1. This strong synergistic effect was also corroborated in the primary MDS patient samples and in an MDS cell line xenograft mouse model. Furthermore, immunohistochemical staining showed that there was more DNA damage accumulation in the combination group than that in any other groups. This is the first report on how the AICAR suppresses MDS cell proliferation and synergizes with decitabine via DNA damage induction. AICAR in combination with decitabine may be a promising therapeutic strategy in MDS.

Citation

Jin Liu, Long Liang, Xin Li, Yuan Liang Peng, Ji Zhang, Xiao Long Wang, Jing Liu, Ling Nie. AICAR suppresses cell proliferation and synergizes with decitabine in myelodysplastic syndrome via DNA damage induction. Biotechnology letters. 2021 Jun;43(6):1131-1142

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PMID: 33788127

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