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Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner.

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  • معلومة اضافية
    • المصدر:
      Publisher: Informa Healthcare Country of Publication: England NLM ID: 8800150 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-2513 (Electronic) Linking ISSN: 08923973 NLM ISO Abbreviation: Immunopharmacol Immunotoxicol Subsets: MEDLINE
    • بيانات النشر:
      Publication: London : Informa Healthcare
      Original Publication: New York, N.Y. : Marcel Dekker, c1987-
    • الموضوع:
      Adenine/*analogs & derivatives ; Benzoquinones/*pharmacology ; HSP90 Heat-Shock Proteins/*antagonists & inhibitors ; Heterocyclic Compounds, 4 or More Rings/*pharmacology ; Isoxazoles/*pharmacology ; Killer Cells, Natural/*metabolism ; Lactams, Macrocyclic/*pharmacology ; Pyridines/*pharmacology ; Resorcinols/*pharmacology; Adenine/pharmacology ; Apoptosis/drug effects ; Cell Survival/drug effects ; Cytokines/metabolism ; Dose-Response Relationship, Drug ; Down-Regulation/drug effects ; Female ; Humans ; Male
    • نبذة مختصرة :
      Heat shock protein 90 (Hsp90) is a ubiquitously expressed ATP-dependent molecular chaperone across all species that helps to the correct the folding of many proteins related to important signaling pathways. Tumor cells expressing Hsp90 have more ATP-binding affinity than normal cells. Many correlative inhibitors have been developed to promising anti-tumor strategies and have been evaluated in clinical trials. However, the effect of Hsp90 inhibitors on immunocytes cannot be ignored. Natural killer (NK) cells are key components of the innate immune system that play a pivotal role in tumor surveillance. The present study has investigated the potential effect of four Hsp90 inhibitors (NVP-AUY922, BIIB021, 17-DMAG, and SNX-2112) on human primary NK cells. The viability, cytotoxicity, apoptosis, phenotype, and cytokine secretion of NK cells after inhibitor treatment were assessed. The results of this study demonstrated that the inhibitors had negative effects on NK cell activity in a dose-dependent manner. The four inhibitors significantly reduced the cytotoxicity of the NK cells by decreasing viability, inducing apoptosis and down-regulating the expression of cytokines and functional receptors. These findings suggest that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy.
    • Contributed Indexing:
      Keywords: Apoptosis; Hsp90 inhibitors; cytotoxicity; human natural killer cells; immunotherapy
    • الرقم المعرف:
      0 (5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide)
      0 (6-chloro-9-(4-methoxy-3,5-dimethylpyridin-2-ylmethyl)-9H-purin-2-ylamine)
      0 (Benzoquinones)
      0 (Cytokines)
      0 (HSP90 Heat-Shock Proteins)
      0 (Heterocyclic Compounds, 4 or More Rings)
      0 (Isoxazoles)
      0 (Lactams, Macrocyclic)
      0 (Pyridines)
      0 (Resorcinols)
      0 (SNX 2112)
      001L2FE0M3 (17-(dimethylaminoethylamino)-17-demethoxygeldanamycin)
      JAC85A2161 (Adenine)
    • الموضوع:
      Date Created: 20151209 Date Completed: 20161213 Latest Revision: 20181202
    • الموضوع:
      20250114
    • الرقم المعرف:
      10.3109/08923973.2015.1119159
    • الرقم المعرف:
      26642940