Abbasi Yusef, Pooladi Marziyeh, Nazmabadi Roya, Amri Jamal, Abbasi Helia, 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.
Cell J. 2024 Feb 1;26(2):121-129. doi: 10.22074/cellj.2024.2016937.1459.
Enhanced cell survival and drug resistance in tumor cells have been linked to the overexpression of antiapoptotic members of the Bcl-2 family proteins, including Bcl-2 and Mcl-1. The aim of this study was to explore the impact of formononetin and dihydroartemisinin combination on the growth and apoptosis of acute myeloid leukemia (AML) cells.
In this experimental study, the cell survival and cell proliferation were tested by MTT assay and trypan blue staining. The evaluation of cell apoptosis was conducted using Hoechst 33342 staining and a colorimetric assay to measure caspase-3 activity. To determine the mRNA levels of Mcl-1, Bcl-2, Bax, and , a quantitative real-time polymerase chain reaction (qRT-PCR) was performed.
We showed that treatment with either formononetin or dihydroartemisinin alone, led to significant decrease in the cell survival and growth, and triggered apoptosis in U937 and KG-1 AML cell lines. Moreover, treatment with each of the compounds alone significantly decreased the mRNA levels of and mRNA, while, the expression level of Bax mRNA was enhanced. Combination of two compounds showed a synergistic anti-cancer effect.
The anti-leukemic potential of formononetin and dihydroartemisinin is exerted through the effect on cell cycle progression and intrinsic pathway of apoptosis. Therefore, they can be considered as a potential anti-leukemic agent alone or along with existing chemotherapeutic drugs.
肿瘤细胞中增强的细胞存活和耐药性与Bcl-2家族蛋白抗凋亡成员（包括Bcl-2和Mcl-1）的过表达有关。本研究的目的是探讨刺芒柄花素与双氢青蒿素联合使用对急性髓系白血病（AML）细胞生长和凋亡的影响。
在本实验研究中，通过MTT法和台盼蓝染色检测细胞存活和增殖情况。使用Hoechst 33342染色和比色法测定caspase-3活性来评估细胞凋亡。为了确定Mcl-1、Bcl-2、Bax和 的mRNA水平，进行了定量实时聚合酶链反应（qRT-PCR）。
我们发现，单独使用刺芒柄花素或双氢青蒿素处理，均可导致U937和KG-1 AML细胞系的细胞存活和生长显著降低，并引发细胞凋亡。此外，单独使用每种化合物处理均显著降低了 和 mRNA的水平，而Bax mRNA的表达水平则增强。两种化合物联合使用显示出协同抗癌作用。
刺芒柄花素和双氢青蒿素的抗白血病潜力是通过对细胞周期进程和细胞凋亡内在途径的影响来发挥的。因此，它们可单独或与现有化疗药物一起被视为潜在的抗白血病药物。
