RRC ID 59938
Author Uchida S, Kobayashi K, Ohno S, Sakagami H, Kohase H, Nagasaka H.
Title Induction of Non-Apoptotic Cell Death by Adrenergic Agonists in Human Oral Squamous Cell Carcinoma Cell Lines.
Journal Anticancer Res
Abstract BACKGROUND/AIM:Although adrenergic agonists have been used in dental treatments and oral surgery for general anesthesia, their cytotoxicity against human oral malignant and non-malignant cell has not been well- understood. The present study was undertaken to investigate the cytotoxicity of five adrenergic agonists against human oral squamous cell carcinoma (OSCC), glioblastoma, promyelocytic leukemia, and normal oral mesenchymal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and normal epidermal keratinocytes.
MATERIALS AND METHODS:Tumor-specificity (TS) was calculated by the ratio between the mean 50% cytotoxic concentration against normal cells to that of tumor cells. Internucleosomal DNA fragmentation was detected using agarose gel electrophoresis. Caspase-3 activity was measured by substrate cleavage.
RESULTS:Both cytotoxicity and tumor-specificity of adrenergic agonists against OSCC cell lines was in the order of isoprenaline>dexmedetomidine> adrenaline>clonidine and phenylephrine. Isoprenaline and dexmedetomidine did not induce apoptosis markers, such as internucleosomal DNA fragmentation and caspase-3 activation, but induced a smear pattern of DNA fragmentation in OSCC cell lines. Their cytotoxicity was not reduced by pretreatment with autophagy inhibitors, or by adrenoceptors antagonists. Addition of superoxide dismutase and catalase significantly reduced the cytotoxicity of isoprenaline, but not that of dexmedetomidine.
CONCLUSION:Isoprenaline and dexmedetomidine induce non-apoptotic cell death by different mechanisms.
Volume 39(7)
Pages 3519-3529
Published 2019-7-1
DOI 10.21873/anticanres.13498
PII 39/7/3519
PMID 31262876
MeSH Adrenergic Agonists / pharmacology* Antineoplastic Agents / pharmacology* Carcinoma, Squamous Cell / drug therapy* Catalase / pharmacology Cell Death / drug effects* Cells, Cultured Child Clonidine / pharmacology DNA Fragmentation Dexmedetomidine / pharmacology Epinephrine / pharmacology Humans Isoproterenol / pharmacology Mouth Neoplasms / drug therapy* Phenylephrine / pharmacology Superoxide Dismutase / pharmacology
IF 1.935
Times Cited 1
Resource
Human and Animal Cells HL-60