Action of tiazofurin and 8-Cl-cAMP in human colon and pancreatic cancer cells.
Tiazofurin and 8-Cl-cAMP are novel chemotherapeutic agents shown to be effective against various cancer cells in vitro and in vivo. They act through distinct mechanisms that might modulate the signal transduction pathway, which causes growth inhibition, differentiation and down-regulation of c-ras and c-myc oncogene expression. We examined the effects of tiazofurin and 8-Cl-cAMP on colony formation of HT-29 human colon cancer and BxPC-3 and PANC-1 human pancreatic cancer cell lines. The IC50 of 8-Cl-cAMP was 0.1 and 0.2 microM in the pancreatic and colon cancer cell lines, respectively, and tiazofurin yielded IC50s from 4 (PANC-1) to 18 microM (HT-29). Simultaneous incubation with 8-Cl-cAMP and tiazofurin had additive effects on the inhibition of colony formation in the three examined cell lines. These results indicate possible clinical usefulness of a combination of tiazofurin and 8-Cl-cAMP in the treatment of colon and pancreatic carcinomas.
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46202-5200.
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D004357:Drug Synergism; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D012254:Ribavirin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D014410:Tumor Stem Cell Assay
D015124:8-Bromo Cyclic Adenosine Monophosphate; D012254:Ribavirin; C044258:8-chloro-cyclic adenosine monophosphate; D007168:IMP Dehydrogenase; C033706:tiazofurin