Abbasi Yusef, Pooladi Marziyeh, Nazmabadi Roya, Amri Jamal, Abbasi Helia, Aghabeygi Razieh, Karami Hadi
Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.
Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.
Int J Mol Cell Med. 2024;13(3):259-271. doi: 10.22088/IJMCM.BUMS.13.3.259.
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 IC 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 suppression of cell growth and survival. Formononetin enhanced the apoptotic effect of ABT-737, with contribution by inhibition of the Mcl-1 expression.
髓系白血病细胞分化蛋白1（Mcl-1）的过表达与ABT-737毒性降低及继发性耐药相关。在本研究中，研究了刺芒柄花素（染料木黄酮B）对急性淋巴细胞白血病（ALL）细胞中Mcl-1表达、细胞生长、凋亡及ABT-737敏感性的影响。在本实验研究中，采用细胞增殖和MTT试验来研究刺芒柄花素对细胞生长和存活的影响。进行qRT-PCR以测量基因表达。使用Hoechst 33342染色和半胱天冬酶-3活性测定来确定细胞凋亡。我们的数据表明，刺芒柄花素和ABT-737均导致IC值显著降低，并且相对于单一处理，二者协同降低细胞生长和存活。用ABT-737处理后发现Mcl-1过表达。刺芒柄花素降低了B细胞淋巴瘤2（Bcl-2）和Mcl-1的表达，并增加了Bcl-2相关蛋白x（Bax）和P21的表达。此外，刺芒柄花素增强了ABT-737对ALL细胞的凋亡作用。总之，刺芒柄花素在人ALL细胞中表现出抗癌活性——抑制细胞生长和存活。刺芒柄花素通过抑制Mcl-1表达增强了ABT-737的凋亡作用。
