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

• Published in: Surgical neurology 2006-05, Vol.65 (5), p.478-484
• Main Authors: Altinoz, Meric A., Bilir, Ayhan, Del Maestro, Rolando F., Tuna, Sevilcan, Ozcan, Emin, Gedikoglu, Gunduz
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis - drug effects; Apoptosis - radiation effects; ATP-Binding Cassette, Sub-Family B, Member 1; Brain tumor; C6 glioma; Cell Line, Tumor; Diltiazem; Diltiazem - pharmacology; Drug Synergism; Glia; Glioma - drug therapy; Glioma - radiotherapy; Humans; Microscopy, Electron; Mitochondria - drug effects; Mitochondria - metabolism; Noscapine; Noscapine - pharmacology; Paclitaxel - pharmacology; Radiation; S Phase - drug effects; S Phase - radiation effects; Taxol; Tumor Stem Cell Assay
• ISSN: 0090-3019; 1879-3339
• DOI: 10.1016/j.surneu.2005.06.024

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. Effects of N (11.1 μmol/L), D (11.1 μmol/L), and T (11.7 μmol/L) were monitored in C6 glioma cells via S phase, colony formation, and fine structure analysis. 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. Noscapine and D should be further tested in animal models because of their potential and already-present clinical applicability.