101. Noscapine and diltiazem augment taxol and radiation-induced S-phase arrest and clonogenic death of C6 glioma in vitro.
- Author
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Altinoz MA, Bilir A, Del Maestro RF, Tuna S, Ozcan E, and Gedikoglu G
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Member 1, Apoptosis radiation effects, Cell Line, Tumor, Drug Synergism, Glioma radiotherapy, Humans, Microscopy, Electron, Mitochondria drug effects, Mitochondria metabolism, S Phase radiation effects, Tumor Stem Cell Assay, Antineoplastic Combined Chemotherapy Protocols pharmacology, Apoptosis drug effects, Diltiazem pharmacology, Glioma drug therapy, Noscapine pharmacology, Paclitaxel pharmacology, S Phase drug effects
- Abstract
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 micromol/L), D (11.1 micromol/L), and T (11.7 micromol/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.
- Published
- 2006
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