Alleviating the progression of acute myeloid leukemia (AML) by sulforaphane through controlling miR-155 levels

• Published in: Molecular biology reports 2018-12, Vol.45 (6), p.2491-2499
• Main Authors: Koolivand, Mohsen, Ansari, Maryam, Piroozian, Fatemeh, Moein, Soheila, MalekZadeh, Kianoosh
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Adolescent; Adult; Aged; Animal Anatomy; Animal Biochemistry; Apoptosis; Apoptosis - drug effects; Biomarkers, Tumor; Biomedical and Life Sciences; Cancer; Cell Differentiation - drug effects; Cell Line, Tumor; Child; Child, Preschool; Disease Progression; Female; Gene Expression Regulation, Leukemic - genetics; Histology; Humans; Isothiocyanates - pharmacology; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Life Sciences; Male; MicroRNAs - drug effects; MicroRNAs - genetics; Middle Aged; miRNA; Morphology; Mortality; Myeloid leukemia; Original Article; Patients; Progenitor cells; Signal Transduction; Stem cells; Sulforaphane
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-018-4416-0

Acute myeloid leukemia (AML) has the highest rate of mortality among the leukemias. Disruption in miRNAs level is involved in the pathogenesis of the disease. The miR-155 has a role in primary differentiation of myeloid progenitor. Meanwhile, there is little knowledge about the effects of sulforaphane against leukemia. The present study tried to evaluate pathologic effect of miR-155 in patients in various subgroups of AML, and then pioneered in assessing miR-155 levels by the effect of sulforaphane in different AML cell lines. The miR-155 level was significantly higher in patients with AML compared to the controls. Interestingly, the increase in miR-155 was converged with raising the subtype of AML (from M1 to M5). The miR-155 levels increased by 1.2 times in patients with M1, but this increase reached 2.5 times in the patients in the M5 subgroup. Sulforaphane reduced the number of live cells and increased the mortality rate of AML cells particularly by induction of apoptosis. However, the anti-proliferative effect of this agent was more dominant and could dose-dependently lessen miR-155 levels in myeloid leukemia cells. More or less, about 80% reduction in miR-155 expression was almost observed after 48 h treatment with 60 µM sulforaphane in all four studied cell lines. The obtained results indicated that miR-155 might function as an oncomir in AML and can potentially be considered as a prognosis biomarker for AML. The anti-cancer effects of sulforaphane can be correlated with reduction of miR-155 levels. These findings suggested that sulforaphane could induce more differentiation in myeloid progenitor cells through controlling the miR-155, thereby mitigating the progress of AML.