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染料木黄酮通过在转录水平上调B细胞易位基因3抑制急性淋巴细胞白血病细胞的增殖。

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

作者信息

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

机构信息

Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom, Iran.

Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

出版信息

Galen Med J. 2019 Mar 26;8:e1229. doi: 10.31661/gmj.v8i0.1229. eCollection 2019.

DOI:10.31661/gmj.v8i0.1229
PMID:34466474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8343482/
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 () 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 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 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 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 as a tumor suppressor gene can be induced by genistein. It seems that 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.

摘要

背景

急性淋巴细胞白血病(ALL)是一种在儿童中高度流行的癌症,约占15岁以下白血病病例的78%。不同研究表明,B细胞易位基因3(BTG3)在不同癌症的进展中起抑制作用。染料木黄酮被认为是一种天然且具有生物相容性的化合物以及一种新型抗癌剂。在本研究中,我们评估了染料木黄酮对ALL癌细胞中BTG3表达及增殖的影响。

材料与方法

ALL细胞系(MOLT4、MOLT17和JURKAT)在标准条件下培养。使用MTT法检测染料木黄酮的细胞毒性。用不同浓度的染料木黄酮(10、25、40和55μM)处理细胞24、48和72小时,然后测量细胞活力和生长速率。应用定量实时聚合酶链反应来研究染料木黄酮对BTG3表达的影响。

结果

与未处理的细胞相比,用染料木黄酮处理的活细胞百分比显著降低,且与染料木黄酮浓度的增加呈负相关。本研究表明40μM的染料木黄酮剂量具有显著的抗癌作用。在转录水平上,染料木黄酮可使MOLT4和JURKAT细胞系中的BTG3升高1.7倍,使MOLT17细胞系中的BTG3升高2.7倍,同时癌细胞增殖速率降低60%至90%。

结论

染料木黄酮可诱导肿瘤抑制基因BTG3上调。似乎BTG3的重新激活可被视为染料木黄酮抗增殖作用的另一种机制,并且可被认为是一种抗血液恶性肿瘤的候选阻滞剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1209/8343482/b3e1d31b2151/gmj-8-e1229-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1209/8343482/7ee90774f72d/gmj-8-e1229-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1209/8343482/525f74fd8643/gmj-8-e1229-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1209/8343482/a0f7170707d1/gmj-8-e1229-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1209/8343482/b3e1d31b2151/gmj-8-e1229-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1209/8343482/7ee90774f72d/gmj-8-e1229-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1209/8343482/525f74fd8643/gmj-8-e1229-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1209/8343482/a0f7170707d1/gmj-8-e1229-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1209/8343482/b3e1d31b2151/gmj-8-e1229-g004.jpg

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本文引用的文献

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Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among North Indian population.印度北部人群中儿童急性淋巴细胞白血病中某些凋亡基因的异常启动子高甲基化
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Understanding genistein in cancer: The "good" and the "bad" effects: A review.了解染料木黄酮在癌症中的作用:“好”与“坏”的影响:综述
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The roles of BTG3 expression in gastric cancer: a potential marker for carcinogenesis and a target molecule for gene therapy.BTG3表达在胃癌中的作用:致癌的潜在标志物及基因治疗的靶分子。
Oncotarget. 2015 Aug 14;6(23):19841-67. doi: 10.18632/oncotarget.3734.
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Genistein-inhibited cancer stem cell-like properties and reduced chemoresistance of gastric cancer.染料木黄酮抑制胃癌的癌症干细胞样特性并降低其化疗耐药性。
Int J Mol Sci. 2014 Feb 25;15(3):3432-43. doi: 10.3390/ijms15033432.
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