Comparative cytotoxicity of C-1311 in colon cancer in vitro and in vivo using the hollow fiber assay.
The aim of this study was to investigate the antiproliferative effects of C-1311 (Symadex), a member of the imidazoacridinone family, in human colorectal cancer cells. In the in vitro screen, C-1311 led to the most prominent growth inhibition in HT29, HCT116, and COLO205 cell lines when compared to oxaliplatin, CPT-11, DFUR, 5-FU and capecitabine. The GI(50)values for C-1311 ranged from 0.12 to 0.83 microM and the TGI concentrations (resulting in total growth inhibition) were 6- to 13-fold lower than those of other agents. In the hollow fiber assay in vivo, C-1311 caused 77% growth inhibition of HT29 in the intraperitoneal site as compared to paclitaxel (17% growth inhibition). In the subcutaneous site, C-1311 produced 57% growth inhibition while paclitaxel showed no cell growth inhibition effects. This unique cytotoxicity profile of C-1311 warrants further investigation and supports its clinical development in colon cancer patients. Symadex (C-1311) is currently in phase 2 clinical trials.
Alami
N
N
Department of Oncology, McGill University, Montreal, QC, Canada.
Paterson
J
J
Belanger
S
S
Juste
S
S
Grieshaber
C K
CK
Leyland-Jones
B
B
D000609:Aminoacridines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D000069287:Capecitabine; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017322:Clinical Trials, Phase II as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D066298:In Vitro Techniques; D000077146:Irinotecan; D051379:Mice; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000494:pharmacology
D000609:Aminoacridines; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; C098965:C 1311; D017239:Paclitaxel; D005472:Fluorouracil; D002166:Camptothecin