Effect of Calcium Channel Blocking Drugs on Tumor Cell Oxygen Utilization
Oxygen tension in tumor tissue can influence the effectiveness of radiation and many chemotherapeutic agents like misonidazole, bleomycin and adriamycin, which kill tumor cells via oxygen-linked metabolic mechanisms. Therefore it is important to improve tumor oxygenation during the course of treatment with either radiation or drugs. Tumor oxygen tension can be influenced by blood flow as well as by the rate of tumor cell oxygen utilization. We have studied the factors that influence tumor cell oxygen utilization (1,2) in vitro and have previously found that pentobarbital sensitizes tumor cells to hyperbaric oxygen breathing (3). Part of the mechanism may involve either inhibition of oxygen utilization or body temperature lowering, which may also produce reoxygenation by inhibition of tumor cell oxygen utilization (4). We have found that the anaesthetic drugs chlorpromazine and stelazine inhibit cellular oxygen utilization (5). The mechanism of action of these drugs may involve alterations in voltage-dependent calcium channels. Therefore we investigated further the possibility that calcium channels were involved in cellular respiration. We have studied the currently used heart attack drugs diltiazem, nifedipine (procardia) and verapamil as well as praziquantel for their effects on tumor cell oxygen utilization in vitro. We have also determined their inhibiting capacity with tumor cells incubated in the presence of succinate and glucose, substrates known to stimulate, in the former case, and to inhibit cellular oxygen utilization in the later case.
KeywordsDioxide Magnesium Respiration Bicarbonate Glutamine
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