ArticleMolecular biology reports2022
Cordycepin enhances hyperthermia-induced apoptosis and cell cycle arrest by modulating the MAPK pathway in human lymphoma U937 cells.
Article in Molecular biology reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Application and research progress of cordycepin in the treatment of tumours (Review).Molecular medicine reports · 2024Review
- Structural and pharmacological insights into cordycepin for neoplasms and metabolic disorders.Frontiers in pharmacology · 2024Review
- The role and mechanisms of cordycepin in inhibiting cancer cells.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Review
- Natural Product Cordycepin (CD) Inhibition for NRP1/CD304 Expression and Possibly SARS-CoV-2 Susceptibility Prevention on Cancers.Microorganisms · 2023Article
- The therapeutic potential of natural products for treating pancreatic cancer.Frontiers in pharmacology · 2022Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundHyperthermia induces cancer cell death. However, the cytotoxic effect of hyperthermia is not sufficient. Cordycepin can also induce apoptosis in cancer cells and enhance the antitumoral activity of irradiation. To examine cordycepin-mediated enhancement of hyperthermia-induced apoptosis, this study investigated the combined effects and apoptotic mechanisms of hyperthermia and cordycepin on human leukemia U937 cells.
methodsCell viability and apoptosis were measured using MTT assays, Hoechst 33342 staining and Annexin V/PI double staining. The distribution of the cell cycle and sub-G1 phase, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were examined by flow cytometry. The expression of related proteins was analyzed by western blotting.
resultsCombined treatment with hyperthermia and cordycepin markedly augmented apoptosis by upregulating Bax and suppressing Bcl-2, Bid and activated caspase 3 and 8 expression, and apoptosis was decreased by Z-VAD-fmk (a pan caspase inhibitor). We also found that the MMP was significantly decreased and excessive ROS generation occurred. The combination treatment also induced arrest in the G2/M phase by downregulating cyclin dependent kinase 1 (CDK1) and cyclin B1 protein expression. Furthermore, it was observed that mitogen-activated protein kinase (MAPK) pathway including ERK, JNK and p38 signals was involved in the induction of apoptosis. The phosphorylated p38 and JNK were increased and ERK phosphorylation was decreased by the combined treatment. In addition, N-acetyl-L-cysteine (NAC) significantly protected the cells by restoring ROS levels and the activity of caspase-3, inactivating the MAPK pathway.
conclusionCordycepin significantly enhanced hyperthermia-induced apoptosis and G2/M phase arrest in U937 cells. The combined treatment enhanced apoptosis through the MAPK pathway and mitochondrial dysfunction, and these effects could be rescued by NAC. We report for the first time that cordycepin can be used as a hyperthermia sensitizer to treat leukemia.
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