A hollow fiber model for in vitro studies of cytotoxic compounds: activity of the cyanoguanidine CHS 828.
The hollow fiber assay is currently used as an in vivo model for anticancer drug screening in nude mice, but it can also be used as an in vitro model. In the current study, an in vitro hollow fiber model was used to study the effect and mode of induced cell death of a new cyanoguanidine, CHS 828. Human leukemia, adenocarcinoma and lymphoma cell lines as well as primary cultures of human tumor cells from patients with chronic lymphocytic leukemia (CLL) and ovarian cancer (OC) and normal human lymphocytes were cultured in semipermeable hollow fibers. The fibers were incubated for 3 or 14 days prior to CHS 828 exposure for 72 h, followed by determination of living cell density by MTT staining. For cell morphology, using harvested cultures on cytospin slides had technical advantages compared to using paraffin sections of the formalin-fixed fibers. CHS 828 showed higher antitumor activity on CLL and normal human lymphocyte cultures compared to OC cultures, and cell lines cultured 3 days were more sensitive than those cultured 14 days. Morphological examination of CHS 828-treated cultures revealed a mixture of apoptosis and necrosis.
Division of Clinical Pharmacology, Uppsala University, Sweden. sadia.hassan@medsci.uu.se
S B
SB
Hassan
M
M
de la Torre
P
P
Nygren
M O
MO
Karlsson
R
R
Larsson
E
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Jonsson
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003486:Cyanides / Q000494:pharmacology*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000473:pathology; D016014:Linear Models; D008214:Lymphocytes / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003486:Cyanides; D006146:Guanidines; C401312:N-(6-chlorophenoxyhexyl)-N''-cyano-N''-4-pyridylguanidine