Enhancement of the Sensitivity of the Acute Lymphoblastic Leukemia Cells to ABT-737 by Formononetin.

IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL International Journal of Molecular and Cellular Medicine Pub Date : 2024-01-01 DOI:10.22088/IJMCM.BUMS.13.3.259

Yusef Abbasi, Marziyeh Pooladi, Roya Nazmabadi, Jamal Amri, Helia Abbasi, Razieh Aghabeygi, Hadi Karami

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Abstract

Overexpression of (myeloid leukemia cell differentiation protein 1) Mcl-1 is associated with the reduction of ABT-737 toxicity and secondary resistance. In this study, the effect of formononetin (biochanin B) on Mcl-1 expression, cell growth, apoptosis, and ABT-737 sensitivity of the acute lymphoblastic leukemia (ALL) cells was investigated. In this experimental study, the cell proliferation and MTT assays were used to investigate the effect of formononetin on cell growth and survival. qRT-PCR was performed for the measurement of gene expression. Hoechst 33342 staining and caspase-3 activity assay were used for the determination of apoptosis. Our data showed that formononetin and ABT-737 both led to a significant reduction in the IC₅₀ value and synergistically reduced the cell growth and survival relative to single treatment. Overexpression of Mcl-1 was found after the treatment with ABT-737. Formononetin decreased the expression of B-cell lymphoma 2 (Bcl-2) and Mcl-1 and increased the Bcl-2-associated protein x (Bax) and P21 expression. Moreover, formononetin enhanced the apoptotic effect of ABT-737 in ALL cells. In summary, formononetin showed anti-carcinogenic activities in human ALL cells via suppression of cell growth and survival. Formononetin enhanced the apoptotic effect of ABT-737, with contribution by inhibition of the Mcl-1 expression.

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福莫西汀提高急性淋巴细胞白血病细胞对 ABT-737 的敏感性

髓性白血病细胞分化蛋白1）Mcl-1的过表达与ABT-737毒性降低和继发性耐药性有关。本研究探讨了福莫西汀（生物黄酮B）对急性淋巴细胞白血病（ALL）细胞的Mcl-1表达、细胞生长、凋亡和ABT-737敏感性的影响。在这项实验研究中，采用细胞增殖和 MTT 试验来研究福莫西汀对细胞生长和存活的影响。Hoechst 33342 染色法和 caspase-3 活性测定法用于确定细胞凋亡。我们的数据显示，福莫西汀和ABT-737都能显著降低IC50值，并协同降低细胞的生长和存活率。ABT-737治疗后发现Mcl-1过度表达。福莫西汀降低了B细胞淋巴瘤2（Bcl-2）和Mcl-1的表达，增加了Bcl-2相关蛋白x（Bax）和P21的表达。此外，福莫西汀还能增强 ABT-737 对 ALL 细胞的凋亡作用。总之，福莫西汀通过抑制细胞生长和存活，在人ALL细胞中显示出抗癌活性。福莫西汀通过抑制 Mcl-1 的表达增强了 ABT-737 的凋亡效应。

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来源期刊

International Journal of Molecular and Cellular Medicine MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.60

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0.00%

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期刊介绍： The International Journal of Molecular and Cellular Medicine (IJMCM) is a peer-reviewed, quarterly publication of Cellular and Molecular Biology Research Center (CMBRC), Babol University of Medical Sciences, Babol, Iran. The journal covers all cellular & molecular biology and medicine disciplines such as the genetic basis of disease, biomarker discovery in diagnosis and treatment, genomics and proteomics, bioinformatics, computer applications in human biology, stem cells and tissue engineering, medical biotechnology, nanomedicine, cellular processes related to growth, death and survival, clinical biochemistry, molecular & cellular immunology, molecular and cellular aspects of infectious disease and cancer research. IJMCM is a free access journal. All open access articles published in IJMCM are distributed under the terms of the Creative Commons Attribution CC BY. The journal doesn''t have any submission and article processing charges (APCs).