Polydatin protects against leukemia by inducing apoptosis and activating autophagy via p38-MAPK pathway.

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.