15,16-Dihydrotanshinone I inhibits the proliferation of MV4-11 by means of apoptosis via antagonizing FLT3-ITD/STAT5/Mcl-1 pathway

Abstract

Till now, the medicines approved for acute myeloid leukemia with internal tandem duplication mutation of FMS-like tyrosine kinase 3 (FLT3-ITD) display not ideal efficacy. This study aimed to evaluate the effects of 15,16-dihydrotanshinone I on FLT3-ITD acute myeloid leukemia cells. The inhibitory effect of this compound against MV4-11 was determined using CCK-8 assay. Western blotting detecting caspase-3, PARP, and annexin V-APC/7-AAD was carried out. Activation of FLT3, STAT5, and Mcl-1 expression was analyzed by western blotting. The results showed that MV4-11 was sensitive toward dihydrotanshinone I in a dose-dependent manner (p<0.05). MV4-11 apoptosis was induced notably after dihydrotanshinone I treatment. Western blotting revealed suppressed activation of FLT3, STAT5 and decreased Mcl-1 (p<0.05). This study suggests that dihydrotanshinone I inhibits MV4-11 proliferation by apoptosis via antagonizing FLT3-ITD/STAT5/Mcl-1 path-way, which might provide a novel therapy for acute myeloid leukemia.

Keywords

• Acute myeloid leukemia
• Apoptosis
• 15,16-Dihydrotanshinone I
• FMS-like tyrosine kinase 3
• Internal tandem duplication