Restraining the Proliferation of Acute Lymphoblastic Leukemia Cells by Genistein through Up-regulation of B-cell Translocation Gene-3 at Transcription Level.

Masoumeh Abedi Nejad,Kianoosh Malekzadeh,Masoomeh Afsa,Mohsen Nikbakht

doi:10.31661/gmj.v8i0.1229

Abstract

Background: Acute lymphoblastic leukemia (ALL) is a highly prevalent pediatric cancer accounting for approximately 78% of leukemia cases in patients younger than 15 years old. Different studies have demonstrated that B-cell translocation gene 3 (BTG3) plays a suppressive role in the progress of different cancers. Genistein is considered a natural and biocompatible compound and a new anti-cancer agent. In this study, we evaluate the effect of genistein on BTG3 expression and proliferation of ALL cancer cells. Materials and Methods: ALL cell lines (MOLT4, MOLT17, and JURKAT) were cultured in standard conditions. Cytotoxicity of genistein was detected using MTT assay. The cells were treated with different concentrations of genistein (10, 25, 40, and 55μM) for 24, 48, and 72 hours, and then cell viability and growth rate were measured. The quantitative real-time polymerase chain reaction was applied to investigate the effect of genistein on BTG3 expression. Results: The percentage of vital cells treated with genistein significantly decreased compared to the non-treated cells, showed an inverse relationship with an increasing genistein concentration. The present study suggests a dose of 40μM for genistein as a potent anticancer effect. Genistein could elevate BTG3 for 1.7 folds in MOLT4 and JURKAT and 2.7 folds in MOLT17 cell lines at transcription level conveged with 60 to 90% reduction in the proliferation rate of cancer cells. Conclusion: Up-regulation of BTG3 as a tumor suppressor gene can be induced by genistein. It seems that BTG3 reactivation can be introduced as another mechanism of anti-proliferative effect of genistein and could be considered as a retardant agent candidate against hematopoietic malignancy.

Highlights

Acute lymphoblastic leukemia (ALL) is the main pediatric cancer in developed countries, and the prevalence rate of the disease is approximately 30 to 45 cases in one million children per year [1]
To evaluate the exposure doses of genistein, a 3-day surviving assay for ALL cell lines (MOLT4, MOLT17, and JURKAT) was conducted
According to the growth curve and its comparison with the non-treated group, 64, 41, and 91% of the proliferation occurred as the result of 10μM genistein effect on the second day of culture in case of MOLT4, MOLT17, and JURKAT cells, respectively

Summary

Introduction

Acute lymphoblastic leukemia (ALL) is the main pediatric cancer in developed countries, and the prevalence rate of the disease is approximately 30 to 45 cases in one million children per year [1]. New DNA technologies such as microarray and next-generation sequencing findings of ALL have shed light on the molecular basis of this disease These discoveries have shown that aberrant changes in genetic and epigenetic in genes such as tumor suppressors can disturb main cellular pathways. Different studies have demonstrated that B-cell translocation gene 3 (BTG3) plays a suppressive role in the progress of different cancers. We evaluate the effect of genistein on BTG3 expression and proliferation of ALL cancer cells. Conclusion: Upregulation of BTG3 as a tumor suppressor gene can be induced by genistein It seems that BTG3 reactivation can be introduced as another mechanism of anti-proliferative effect of genistein and could be considered as a retardant agent candidate against hematopoietic malignancy. It seems that BTG3 reactivation can be introduced as another mechanism of anti-proliferative effect of genistein and could be considered as a retardant agent candidate against hematopoietic malignancy. [GMJ.2019;8:e1229] DOI:10.31661/gmj.v8i0.1229

Methods

Results

Discussion

Conclusion