ReferenceID 4513
Icaritin inhibits PLK1 to activate DNA damage response in NK/T cell lymphoma and increases sensitivity to GELOX regime
Mol Ther Oncolytics
Natural killer/T cell lymphoma (NKTCL) is a highly aggressive subtype of non-Hodgkin lymphoma. Gemcitabine, oxaliplatin, and L-asparaginase (GELOX) is one of the first-line chemotherapy regimens of NKTCL. Yet, the progno
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- Reference Id
- 4513
- Evidence Id
- 21103
- Core Evidence Id
- 21103
- Source Reference Id
- 2303
- Herb2 Reference Id
- HBREF003100
- Subject Paper Key
- HBIN016163_35663228
- Pubmed Id
- 35663228
- Doi
- 10.1016/j.omto.2022.04.012
- Paper Title
- Icaritin inhibits PLK1 to activate DNA damage response in NK/T cell lymphoma and increases sensitivity to GELOX regime
- Paper Abstract
- Natural killer/T cell lymphoma (NKTCL) is a highly aggressive subtype of non-Hodgkin lymphoma. Gemcitabine, oxaliplatin, and L-asparaginase (GELOX) is one of the first-line chemotherapy regimens of NKTCL. Yet, the prognosis of NKTCL is poor. Icaritin is an herb-derived monomer from icariin with antitumor effects. We found that icaritin induced proliferation inhibition and apoptosis of NKTCL both in vitro and in vivo . Moreover, icaritin inhibited the dissemination of NKTCL in vivo . RNA sequencing revealed the Polo-like kinase 1 (PLK1) gene and DNA damage response (DDR) as the targets of icaritin. Mechanistically, icaritin inhibited PLK1 to promote checkpoint kinase 2 (Chk2) homodimerization and its T387 phosphorylation, which further activated p53, leading to the activation of the DDR pathway. Moreover, inhibiting PLK1 increased Forkhead box O3a nuclear localization, the latter of which activated ataxia telangiectasia mutated (ATM), an early sensor of DNA damage. Then ATM phosphorylated Chk2 T68 and initiated Chk2 activation. Remarkably, the combined treatment of icaritin and GELOX achieved better antitumor efficacy than single treatment in vivo . In summary, our results proved the efficacy of icaritin treating NKTCL, provided insights into its antitumor molecular mechanism, and revealed the application value of icaritin in facilitating clinical NKTCL treatment.
- Journal
- Mol Ther Oncolytics
- Publish Year
- 2022
- Experiment Subject
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Ataxia Telangiectasia; Non-hodgkin Lymphoma; Natural Killer/t Cell Lymphoma
- Paper Title Cn
- Paper Title En
- Icaritin inhibits PLK1 to activate DNA damage response in NK/T cell lymphoma and increases sensitivity to GELOX regime
- Bilingual Status
- semi_complete