Induction of Non-Apoptotic Cell Death by Adrenergic Agonists in Human Oral Squamous Cell Carcinoma Cell Lines
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Updated: Jan 22, 2026
Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma
Published on: July 25, 2011
Shigenori Uchida1, Katsue Kobayashi2, Seika Ohno3
1Division of Dental Anesthesiology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan sashichitaru930@dent.meikai.ac.jp sakagami@dent.meikai.ac.jp.
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.
Insights
Isoprenaline and dexmedetomidine exhibit cytotoxicity against oral squamous cell carcinoma (OSCC) by inducing non-apoptotic cell death. These adrenergic agonists demonstrate distinct mechanisms of action, impacting cancer cell viability differently.
Area of Science:
- Pharmacology
- Cell Biology
- Oncology
Background:
- Adrenergic agonists are used in dental procedures but their cytotoxicity on oral cells is poorly understood.
- Investigating the effects of adrenergic agonists on various human oral cell lines is crucial.
Purpose of the Study:
- To evaluate the cytotoxicity of five adrenergic agonists against human oral squamous cell carcinoma (OSCC) and normal oral cells.
- To determine the tumor-specificity of these agents.
Main Methods:
- Cytotoxicity was assessed using 50% cytotoxic concentration (CC50) values.
- Apoptosis was detected via DNA fragmentation and caspase-3 activity assays.
- Tumor-specificity (TS) was calculated as the ratio of CC50 in normal cells to tumor cells.
Main Results:
- Isoprenaline and dexmedetomidine showed the highest cytotoxicity and tumor-specificity against OSCC cells.
- These agents induced DNA fragmentation but not classical apoptosis markers.
- Cytotoxicity was independent of autophagy or adrenoceptor antagonism, with isoprenaline's effect linked to reactive oxygen species.
Conclusions:
- Isoprenaline and dexmedetomidine induce non-apoptotic cell death in OSCC.
- Distinct mechanisms underlie the cytotoxicity of isoprenaline and dexmedetomidine.
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