title: Polydatin-induced cell apoptosis and cell cycle arrest are potentiated by Janus kinase 2 inhibition in leukemia cells.
abstract: Polydatin (PD), a natural precursor of resveratrol, has a variety of biological activities, including anti‑tumor effects. However, the underlying molecular mechanisms of the anti-cancer activity of PD has not been fully elucidated. The present study demonstrated that PD significantly inhibited the proliferation of the MOLT-4 leukemia cell line in a dose‑ and time-dependent manner by using Cell Counting Kit‑8 assay. PD also dose-dependently increased the apoptotic rate and caused cell cycle arrest in S phase in MOLT‑4 cells, as revealed by flow cytometry. In addition, PD dose-dependently decreased the mitochondrial membrane potential and led to the generation of reactive oxygen species in MOLT-4 cells. Western blot analysis revealed that the expression of anti‑apoptotic protein B-cell lymphoma 2 (Bcl-2) was decreased, whereas that of pro‑apoptotic protein Bcl‑2‑associated X was increased by PD. Furthermore, the expression of two cell cycle regulatory proteins, cyclin D1 and cyclin B1, was suppressed by PD. Of note, the pro‑apoptotic and cell cycle‑inhibitory effects of PD were potentiated by Janus kinase 2 (JAK2) inhibition. In conclusion, the results of the present study strongly suggested that PD is a promising therapeutic compound for the treatment of leukemia, particularly in combination with JAK inhibitors.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Cao
authors.affiliation: Department of Endodontics, The Fourth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Ding-Ming
authors.initials: DM
authors.lastname: Wan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056744:Cyclin B1 / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D056744:Cyclin B1; D005960:Glucosides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D013267:Stilbenes; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D053614:Janus Kinase 2; C058229:polydatin