Genistein exerts anti-leukemic effects on genetically different acute myeloid leukemia cell lines by inhibiting protein synthesis and cell proliferation while inducing apoptosis – molecular insights from an iTRAQ™ quantitative proteomics study
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https://doi.org/10.18632/oncoscience.120
Karthik Narasimhan1,*, Yew Mun Lee1,*, Teck Kwang Lim1, Sarah Alexandra Port1, Jin-Hua Han1, Chien-Shing Chen2,3 and Qingsong Lin1
1 Department of Biological Sciences, National University of Singapore, Singapore
2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
3 Division of Hematology and Oncology, School of Medicine, Loma Linda University, Loma Linda, California, United States of America
* These authors contributed equally to this work
Correspondence:
Qingsong Lin, email:
Keywords: Acute myeloid leukemia, genistein, mTOR, quantitative proteomics
Received: March 06, 2014 Accepted: February 05, 2015 Published: February 06, 2015
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.
