Zhang Wenhui, Liu Zhongwen, Hao Peiyuan, Zhang Ping, Pei Xiaohang, Shi Mingyue, Zhu Zunmin
Department of Hematology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, 450002, Henan, China.
Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Fuwai Central China Cardiovascular Hospital, Zhengzhou, 450002, Henan, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 14. doi: 10.1007/s00210-025-04160-5.
The clinical treatment of acute myeloid leukemia (AML) remains suboptimal, necessitating the exploration of novel therapeutic strategies. Polydatin, a major active component of the Chinese herb Polygonum cuspidatum, exhibits multiple antitumor properties. However, its potential anti-AML effects and underlying mechanisms remain unclear. In this study, MOLM-13 cells, a representative cell line for AML, were treated with polydatin, and its effects on cell proliferation, cell cycle, apoptosis, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (Δψm) were assessed using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The expression levels of key apoptotic and autophagic markers, including death receptors (DR4 and DR5), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), Bcl-2, Bax, LC3, Beclin1, and P62, were analyzed by western blotting. Furthermore, autophagy levels were evaluated using GFP-LC3 fluorescence and monodansylcadaverine staining. To elucidate the relationship between polydatin and autophagy, the autophagy inhibitor 3-MA and the p38-MAPK activator SB203580 were employed. Polydatin significantly inhibited AML cell proliferation, induced apoptosis and autophagic flux, caused cell cycle arrest in the S phase, reduced Δψm, and promoted ROS generation. Following polydatin treatment, the protein expression levels of DR4, TRAIL, Bax, LC3, and Beclin1 were significantly increased, while DR5, Bcl-2, and P62 were markedly reduced. Additionally, SB203580 promoted polydatin's effects on cell proliferation inhibition, ROS generation, and autophagic flux, whereas 3-MA reversed these effects. These findings demonstrate that polydatin exerts anti-leukemic effects by inhibiting cell proliferation and inducing apoptosis through the activation of autophagy via the p38-MAPK pathway in MOLM-13 AML cells. This suggests that polydatin could serve as a potential therapeutic agent for AML.
急性髓系白血病（AML）的临床治疗效果仍不尽人意，因此有必要探索新的治疗策略。虎杖苷是中药虎杖的主要活性成分，具有多种抗肿瘤特性。然而，其潜在的抗AML作用及相关机制尚不清楚。在本研究中，用虎杖苷处理AML代表性细胞系MOLM-13细胞，并用细胞计数试剂盒-8（CCK-8）检测法和流式细胞术评估其对细胞增殖、细胞周期、凋亡、活性氧（ROS）生成及线粒体膜电位（Δψm）的影响。通过蛋白质免疫印迹法分析关键凋亡和自噬标志物的表达水平，包括死亡受体（DR4和DR5）、肿瘤坏死因子相关凋亡诱导配体（TRAIL）、Bcl-2、Bax、微管相关蛋白1轻链3（LC3）、Beclin1和P62。此外，使用绿色荧光蛋白-LC3（GFP-LC3）荧光和单丹磺酰尸胺染色评估自噬水平。为阐明虎杖苷与自噬的关系，使用了自噬抑制剂3-甲基腺嘌呤（3-MA）和p38丝裂原活化蛋白激酶（p38-MAPK）激活剂SB203580。虎杖苷显著抑制AML细胞增殖，诱导凋亡和自噬流，使细胞周期阻滞于S期，降低Δψm，并促进ROS生成。虎杖苷处理后，DR4、TRAIL、Bax、LC3和Beclin1的蛋白表达水平显著升高，而DR5、Bcl-2和P62明显降低。此外，SB203580增强了虎杖苷对细胞增殖抑制、ROS生成和自噬流的作用，而3-MA则逆转了这些作用。这些结果表明，虎杖苷通过抑制细胞增殖并通过p38-MAPK途径激活自噬诱导凋亡，从而发挥抗白血病作用。这表明虎杖苷可能成为AML的一种潜在治疗药物。
