Acute promyelocytic leukemia (APL) is a specific subtype of acute myelogenous leukemia (AML) characterized by the proliferation of abnormal promyelocytes. Realgar, a Chinese medicine containing arsenic, can be taken orally. Traditional Chinese medicine physicians have employed realgar to treat APL for over a thousand years. Therefore, realgar may be a promising candidate for the treatment of APL. Nevertheless, the underlying mechanism behind realgar therapy is largely unclear. The present study aimed to investigate the effect of realgar on cell death in the APL cell line (NB4) in vitro and to elucidate the underlying mechanism. In this study, after APL cells were treated with different concentrations of realgar, the cell survival rate, apoptotic assay, morphological changes, ATP levels and cell cycle arrest were assessed. The expression of Bcl-2, Bax, Cytochrome C (Cyt-C) and apoptosis-inducing factor (AIF) at the mRNA and protein levels were also measured by immunofluorescence, quantitative PCR (qPCR) and Western blotting. We found that realgar could significantly inhibit APL cell proliferation and cell death in a time- and dose-dependent manner. Realgar effectively decreased the ATP levels in APL cells. Realgar also induced APL cell cycle arrest at the S and G2/M phases. Following realgar treatment, the mRNA and protein levels of Bcl-2 were significantly downregulated, whereas the levels of Bax, Cyt-C, and AIF were significantly upregulated. In summary, realgar can induce APL cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway, suggesting that realgar may be an effective therapeutic for APL.

中文翻译：

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中药雄黄 (As4S4) 在体外通过 Bcl-2/Bax/Cyt-C/AIF 信号通路诱导急性早幼粒细胞白血病细胞死亡

急性早幼粒细胞白血病 (APL) 是急性髓性白血病 (AML) 的一种特殊亚型，其特征是异常早幼粒细胞的增殖。雄黄是一种含砷的中药，可以内服。中医使用雄黄治疗 APL 已有一千多年的历史。因此，雄黄可能是治疗 APL 的有前途的候选药物。然而，雄黄治疗背后的潜在机制在很大程度上尚不清楚。本研究旨在研究雄黄对体外APL细胞系（NB4）细胞死亡的影响。并阐明潜在的机制。在这项研究中，APL 细胞用不同浓度的雄黄处理后，评估了细胞存活率、凋亡测定、形态学变化、ATP 水平和细胞周期停滞。还通过免疫荧光、定量 PCR (qPCR) 和蛋白质印迹法测量了 Bcl-2、Bax、细胞色素 C (Cyt-C) 和凋亡诱导因子 (AIF) 在 mRNA 和蛋白质水平上的表达。我们发现雄黄能以时间和剂量依赖性方式显着抑制APL细胞增殖和细胞死亡。雄黄有效地降​​低了 APL 细胞中的 ATP 水平。雄黄还在 S 和 G2/M 期诱导 APL 细胞周期停滞。雄黄处理后，Bcl-2 的 mRNA 和蛋白水平显着下调，而 Bax、Cyt-C、和 AIF 显着上调。综上所述，雄黄可通过Bcl-2/Bax/Cyt-C/AIF信号通路诱导APL细胞死亡，提示雄黄可能是治疗APL的有效药物。