title: An anticancer drug-sensitive murine erythroleukemia clone: implications for the mechanism of action of antineoplastic drugs.
abstract: The mechanism(s) by which anticancer drugs kill tumor cells remains obscure. The studies reported here were undertaken with the view that the mechanism may be understood in part through an analysis of anticancer drug-sensitive clones. We have isolated a murine (Friend) erythroleukemia clone in which drug sensitivity was correlated with increased differentiation, suggesting that anticancer drug-induced cell death may be based on differentiation or a differentiation-dependent mechanism. In addition, this clone showed a high propensity for constitutive differentiation and frequent appearance of large multinucleate cells. Morphologically similar large aberrant cells were observed after the treatment of parental (745A) cells with Adriamycin (or bleomycin). We attribute these morphological defects occurring in clone 3-1 or in the parental cell line after anticancer drug treatment to a defective or inhibited cell cycle function. We suggest that the putative cell cycle defect in clone 3-1 is coupled to the increased drug-induced differentiation and resulting cell death. From a broader perspective, the studies reported here suggest that the search for and design of new anticancer drugs be directed at agents that modulate differentiation functions.
authors: Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
authors: R D
authors: RD
authors: Dinnen
authors: C F
authors: CF
authors: Robinow
authors: K
authors: K
authors: Ebisuzaki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D014750:Vincristine / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D014750:Vincristine