title: In-vitro schedule-dependency of eo9 and miltefosine in comparison to standard drugs in colon-cancer cells.
abstract: In vitro screening of new antitumor drugs is often limited to fast chemosensitivity assays. The potency of drugs is studied by measuring growth inhibition at the end of the assay after a fixed drug exposure time. In this study, the human colon cancer cell lines HT29 and SW620, were exposed to drugs for 1 h, 24 h (followed by culture in drug-free medium), 72 h and for 72 h with drug renewal every 24 h. Growth inhibition was evaluated at 48 and 72 h after initial drug addition, using the sulforhodamine B (SRB) assay. Chemosensitivity profiles of the investigational drugs EO9, a bioreductive alkylator, and the ether lipid miltefosine (HPC), were compared to those of drugs with different mechanisms of action: doxorubicin, cisplatin (DDP) and 5-fluorouracil. HPC displayed recovery from growth inhibition, in both cell lines, after drug exposures of 1 and 24 hours. DDP showed an increase for both cell lines (p < 0.05) of growth inhibition when drug was being refreshed every 24 h, compared to 72 h continuous drug exposure. Doxorubicin, 5-fluorouracil and EO9 were more potent in SW620 cells. These data suggest that more initial information can be obtained from drug screening assays, when both continuous and short-term drug exposures are studied, instead of one fixed drug exposure time, and indicates that daily renewal of drugs, may reveal possible drug stability and availability problems.
authors.affiliation: FREE UNIV AMSTERDAM HOSP,DEPT ONCOL,POB 7057,1007 MB AMSTERDAM,NETHERLANDS.
authors.forename: J
authors.initials: J
authors.lastname: Vanarkotte
authors.forename: G
authors.initials: G
authors.lastname: Peters
authors.forename: P
authors.initials: P
authors.lastname: Pizao
authors.forename: Y
authors.initials: Y
authors.lastname: Keepers
authors.forename: G
authors.initials: G
authors.lastname: Giaccone