Wu Pei-Shan, Yen Jui-Hung, Chen Pei-Yi, Wu Ming-Jiuan
Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717301, Taiwan.
Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970374, Taiwan.
Int J Mol Sci. 2025 May 31;26(11):5317. doi: 10.3390/ijms26115317.
Biochanin A, a naturally occurring isoflavone derived from legumes, possesses anti-inflammatory, estrogenic, and anticancer activities. In this study, we investigated the cytotoxic effects and underlying molecular mechanisms of Biochanin A in acute myeloid leukemia (AML) cell lines, U937 and THP-1, using in vitro cytotoxicity assays, RNA sequencing, and bioinformatic analyses. Biochanin A induced dose-dependent apoptosis, as evidenced by caspase-7 activation and PARP1 cleavage. Over-representation analysis (ORA) revealed that differentially expressed genes (DEGs) were significantly enriched in pathways related to inflammatory responses, DNA replication, and cell cycle regulation. Gene set enrichment analysis (GSEA) further confirmed the upregulation of apoptosis- and inflammation-related pathways and the downregulation of MYC targets, cholesterol biosynthesis, and G2/M checkpoint gene sets. RT-qPCR analysis demonstrated that Biochanin A downregulated oncogenes such as , , and while upregulating (), (), and (), contributing to apoptosis and cell cycle arrest across both cell lines. Notably, Biochanin A downregulated and in THP-1 cells, indicating a disruption of mitotic progression and epigenetic regulation. In contrast, in U937 cells, Biochanin A upregulated and downregulated , highlighting the involvement of oxidative stress and G1/S cell cycle arrest. These findings support the potential of Biochanin A as a promising therapeutic candidate for AML through both shared and distinct regulatory pathways.
染料木黄酮是一种天然存在的源自豆类的异黄酮，具有抗炎、雌激素样和抗癌活性。在本研究中，我们使用体外细胞毒性试验、RNA测序和生物信息学分析，研究了染料木黄酮对急性髓系白血病（AML）细胞系U937和THP-1的细胞毒性作用及其潜在的分子机制。染料木黄酮诱导剂量依赖性凋亡，这通过半胱天冬酶-7激活和PARP1裂解得以证明。过度表达分析（ORA）显示，差异表达基因（DEGs）在与炎症反应、DNA复制和细胞周期调控相关的通路中显著富集。基因集富集分析（GSEA）进一步证实了凋亡和炎症相关通路的上调以及MYC靶点、胆固醇生物合成和G2/M检查点基因集的下调。RT-qPCR分析表明，染料木黄酮下调了诸如 、 和 等癌基因，同时上调了 （）、 （）和 （），促成了两种细胞系中的细胞凋亡和细胞周期停滞。值得注意的是，染料木黄酮下调了THP-1细胞中的 和 ，表明有丝分裂进程和表观遗传调控受到破坏。相比之下，在U937细胞中，染料木黄酮上调了 并下调了 ，突出了氧化应激和G1/S细胞周期停滞的参与。这些发现支持了染料木黄酮通过共同和独特的调控途径成为AML有前景的治疗候选药物的潜力。
