Realgar (As(4)S(4)), a traditional Chinese medicine, induces acute promyelocytic leukemia cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway in vitro.
Realgar (As(4)S(4)), a traditional Chinese medicine, induces acute promyelocytic leukemia cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway in vitro.
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雄黄 (As4S4) 是一种中药，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。
DOI：
10.18632/aging.204281
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发表时间：
2022-09-12
期刊：
影响因子：
5.2
通讯作者：
Xu, Ruirong
中科院分区：
文献类型：
--
作者：
Li, Zonghong;Zhang, Ruiming;Yin, Xuewei;Li, Nana;Cui, Siyuan;Wang, Teng;Tan, Xing;Shen, Mingyue;Guo, Yun;Wang, Jinxin;Guo, Dadong;Xu, Ruirong
急性早幼粒细胞白血病（APL）是急性髓性白血病（AML）的一种特异性亚型，其特征是异常早幼粒细胞的增殖。雄黄是一种含砷的中药，可以口服。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的一个有希望的候选者。然而，雄黄治疗背后的潜在机制在很大程度上尚不清楚。本研究旨在探讨雄黄对APL细胞株（NB4）细胞死亡的影响，并探讨其作用机制。本研究以不同浓度雄黄处理APL细胞后，观察细胞存活率、凋亡测定、形态学变化、ATP水平和细胞周期阻滞。采用免疫荧光法、定量PCR法和Western blotting法检测Bcl-2、Bax、细胞色素C （Cyt-C）和凋亡诱导因子（AIF） mRNA和蛋白水平的表达。我们发现雄黄能显著抑制APL细胞增殖和细胞死亡，且呈时间和剂量依赖性。雄黄能有效降低APL细胞的ATP水平。雄黄诱导APL细胞周期阻滞在S期和G2/M期。雄黄处理后，Bcl-2 mRNA和蛋白水平显著下调，Bax、Cyt-C和AIF水平显著上调。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。
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.
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