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 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.


CONCLUSIONS
Noscapine and D should be further tested in animal models because of their potential and already-present clinical applicability.
Altinoz
Meric A
MA
Golden Horn (Halic) University, Capa, Istanbul 34390, Turkey. maltinoz@gmail.com
Bilir
Ayhan
A
Del Maestro
Rolando F
RF
Tuna
Sevilcan
S
Ozcan
Emin
E
Gedikoglu
Gunduz
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor; D004110:Diltiazem / Q000494:pharmacology*; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009665:Noscapine / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects* / Q000528:radiation effects; D014410:Tumor Stem Cell Assay
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009665:Noscapine; D004110:Diltiazem; D017239:Paclitaxel