Abstract
Acute myeloid leukemia (AML) is a form of cancer that affects the hematopoietic precursor cells with lethal effects. We investigated the prospect of using genistein as an effective alternate therapy for AML. A two-cell line model, one possessing the FLT3 gene with the ITD mutation (MV4-11) and the other with the wildtype FLT3 gene (HL-60) has been employed. Our 8-plexed iTRAQ™-based quantitative proteomics analysis together with various functional studies demonstrated that genistein exerts anti-leukemic effects on both the AML cell lines. Genistein treatment on the AML cells showed that the drug arrested the mTOR pathway leading to down-regulation of protein synthesis. Additionally, genistein treatment is found to induce cell death via apoptosis. Contrasting regulatory effects of genistein on the cell cycle of the two cell lines were also identified, with the induction of G2/M phase arrest in HL-60 cells but not in MV4-11 cells. Hence, our study highlights the potent anti-leukemic effect of genistein on AML cells irrespective of their genetic status. This suggests the potential use of genistein as an effective general drug therapy for AML patients.
Highlights
Acute myeloid leukemia (AML) is the cancer in leukocytes of myeloid lineage, distinguished by uncontrolled proliferation of hematopoietic precursor cells with decreased rate of self-destruction and impaired differentiation
We showed that genistein exhibited cytotoxicity on both MV4-11 and HL-60 cells in vitro
We have characterized the effects of genistein on AML in a comprehensive manner using a two-cell line model
Summary
Acute myeloid leukemia (AML) is the cancer in leukocytes of myeloid lineage, distinguished by uncontrolled proliferation of hematopoietic precursor cells with decreased rate of self-destruction and impaired differentiation. It comprises of a heterogeneous spectrum of malignancies classified into various genetic abnormalities and clinical characteristics, leading to variable outcomes by current treatments: 20-75% success rates in patients younger than 60 years and < 10% in elderly patients [1,2,3]. Profound myelosuppression, heavy side effects, frequent cancer relapse, poor therapeutic response, and development of resistance to the administered drugs are common deterrents to current treatment strategies.
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