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

Surgical Neurology
Meric A AltinozGunduz Gedikoglu

Abstract

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 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. 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 an...Continue Reading

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Citations

Jul 22, 2008·International Journal of Radiation Oncology, Biology, Physics·Elizabeth W NewcombSilvia C Formenti
Jul 12, 2019·Neurochemical Research·Meric A Altinozİlhan Elmaci
Nov 28, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Divya MuthiahRichard Callaghan
Sep 4, 2008·Anti-cancer Drugs·Gyong-Suk KangEldon E Geisert
Jul 31, 2020·International Journal of Molecular Sciences·Barbora VitovcovaEmil Rudolf

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