Noscapine and diltiazem augment taxol and radiation-induced S-phase arrest and clonogenic death of C6 glioma in vitro

Background: Radiation therapy after surgical resection is the approved treatment of gliomas, and survival benefits are reported with taxane-based chemotherapy. We investigated whether these regimes could be augmented with blood-brain barrier permeable drugs, N and D. Noscapine is an opioid antitussive, which acts anti cancer via blocking microtubule dynamics. Diltiazem is a calcium channel-blocking cardiac antiarrythmic, which also blocks tumor growth and P-glycoprotein. Methods: Effects of N (11.1 mu mol/L), D (11.1 mu mol/L), and T (11.7 mu mol/L) were monitored in C6 glioma cells via S phase, colony formation, and fine structure analysis. Results: Taxol depleted S phase from 35.2% to 12.2%. Both N and D synergistically augmented T-mediated S-phase depletion, and they also effectively reduced colonies, which were more potent by N by 49%. Taxol reduced colonies by 98%, and there were almost no surviving colonies in copresence of T with either N or D. Colony reduction by radiotherapy was increased strongly by T and significantly by N. Taxol and radiation profoundly increased number of mitochondria. Both D and N suppressed this increase via myelinosis and autophagy. Conclusion: Noscapine and D should be further tested in animal models because of their potential and already-present clinical applicability. (c) 2006 Published by Elsevier Inc.