Autophagy-inducing activity of anesthetics against various malignant cells

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Anesthetics have been administered to malignant tumors and surrounding tissues during the surgery, their effects on oral tissues is not well understood. In the present studies, the cytotoxicity of 1) local anesthetics, such as dibucaine 2) intravenous anesthetics, such as midazolam and 3) adrenergic agonists, such as dexmedetomidine against oral tumor and normal cells was compared among each group. Tumor-specificity index was determined by the ratio of mean 50% cytotoxic concentration against normal cells to that for tumor cells. Apoptosis induction was monitored by internucleosomal DNA fragmentation and caspase-3,-8, and-9 activation. Fine cell structure was observed under transmission electron microscopy. Dibucaine, midazolam and dexmedetomodine did not induce apoptosis in oral squamous cell carcinoma(OSCC) cells although they induced apoptosis in HL-60(human promyelocytic leukemia). Autophagy inhibitors did not reduce the cytotoxicity induced by these drugs. The necrosis may be involved in the induction of antitumor activity by local anesthetics, intravenous anesthetics and adrenergic agonists in OSCC cells. However, further study is needed for another tumor cell lines