Chen Pengjie, Yu Li, Yang Rui, Zeng Wen, Chen Yanxi, Wang Fengmei, Xu Yonggang, Yang Xiupeng
Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
Curr Issues Mol Biol. 2025 Apr 7;47(4):253. doi: 10.3390/cimb47040253.
Myelodysplastic syndrome (MDS) is a heterogeneous myeloid clonal disorder that represents a significant threat to human health. AsS, a natural compound, has been shown to exert therapeutic effects on various malignant tumors, including acute myeloid leukemia (AML), breast cancer, and osteosarcoma, based on extensive clinical experience. In this study, we investigated the mechanism by which AsS inhibits the proliferation of the myelodysplastic syndrome (MDS) SKM-1 cell line. Our findings revealed that AsS inhibited the proliferation of SKM-1 cells in a time- and dose-dependent manner. Flow cytometry, protein immunoblotting, and real-time fluorescence quantitative PCR analyses demonstrated that AsS promotes the phosphorylation of P38 MAPK, thereby activating the MAPK signaling pathway. Additionally, it promotes apoptosis by increasing the BAX/Bcl-2 ratio and induces S-phase arrest through the downregulation of the cell cycle-related protein cyclin A2. Further studies demonstrated that AsS-treated cells exhibited ROS accumulation under fluorescence microscopy, along with activation of the P38 MAPK signaling pathway, increased apoptosis, and S-phase arrest in the cell cycle. This process could be partially reversed by the ROS inhibitor N-acetylcysteine. Therefore, the results of the present study suggest that AsS induces ROS accumulation in SKM-1 cells, which contributes to the activation of the P38 MAPK signaling pathway, promoting apoptosis and S-phase arrest in the cell cycle. Additionally, AsS may serve as a potent therapeutic agent for the treatment of myelodysplastic syndromes, with ROS acting as one of the key therapeutic targets.
骨髓增生异常综合征（MDS）是一种异质性髓系克隆性疾病，对人类健康构成重大威胁。基于广泛的临床经验，天然化合物AsS已被证明对包括急性髓系白血病（AML）、乳腺癌和骨肉瘤在内的多种恶性肿瘤具有治疗作用。在本研究中，我们探究了AsS抑制骨髓增生异常综合征（MDS）SKM-1细胞系增殖的机制。我们的研究结果显示，AsS以时间和剂量依赖性方式抑制SKM-1细胞的增殖。流式细胞术、蛋白质免疫印迹和实时荧光定量PCR分析表明，AsS促进P38丝裂原活化蛋白激酶（P38 MAPK）的磷酸化，从而激活丝裂原活化蛋白激酶（MAPK）信号通路。此外，它通过增加BAX/Bcl-2比值促进细胞凋亡，并通过下调细胞周期相关蛋白细胞周期蛋白A2诱导S期阻滞。进一步的研究表明，在荧光显微镜下，经AsS处理的细胞表现出活性氧（ROS）积累，同时伴有P38 MAPK信号通路的激活、细胞凋亡增加和细胞周期S期阻滞。该过程可被ROS抑制剂N-乙酰半胱氨酸部分逆转。因此，本研究结果表明，AsS诱导SKM-1细胞中ROS积累，这有助于激活P38 MAPK信号通路，促进细胞凋亡和细胞周期S期阻滞。此外，AsS可能作为治疗骨髓增生异常综合征的有效治疗药物，其中ROS作为关键治疗靶点之一。
