title: In vitro cytotoxicity of Phortress against colorectal cancer.
abstract: Phortress is a novel benzothiazole compound with activity concentrated in certain breast, ovarian and renal cancer cell lines. Its anti-angiogenic effects are unknown. In this study, the in vitro anti-angiogenic effects of Phortress were screened for and results compared with two control drugs, paclitaxel and fumagillin. in vitro anti-angiogenic activity was examined by MTS assays, growth curves and clonogenic survival assays on human umbilical vein endothelial cells (HUVEC). In addition and as a comparator, effects were examined on MRCV fibroblasts and also the MCF7 breast cancer cell line, shown to be sensitive on the NCI60 panel and 3 colorectal cancer cell lines (HT29, SW480 and SW620) that were reportedly insensitive. Effects on endothelial tube differentiation were assessed by the Matrigel assay. Phortress had no effect on HUVEC and MRCV cell proliferation and survival. Unlike paclitaxel and fumagillin, Phortress did not inhibit endothelial tube differentiation. Phortress therefore exhibits no in vitro anti-angiogenic activity. As expected, Phortress was cytotoxic to MCF7 breast cancer cells, but unexpectedly, Phortress was also potent against colorectal cancer cells in clonogenic survival and cell growth (growth curves but not MTS assay) end-points. The efficacy of Phortress against colorectal cancer cells in the current study confirms that the spectrum of activity of Phortress may be wider than previously thought.
authors.affiliation: Department of Oncology, University of Nottingham, City Hospital, Nottingham, NG5 1PB, UK.
authors.forename: Abhik
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Stewart Graham
authors.initials: SG
authors.lastname: Martin
mesh_terms: D001681:Biological Assay; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003510:Cyclohexanes / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D011355:Prodrugs; D012717:Sesquiterpenes; D013844:Thiazoles; C026211:fumagillin; C492651:Phortress; D017239:Paclitaxel