The linking of anticancer drugs, cell cycle blocks, and differentiation: implications in the search for antineoplastic drugs.
The quest for anticancer drugs has been primarily directed at agents that interfere with cell replication, yet the basis for drug-induced cytotoxicity remains unsolved. In our previous studies we noted a relationship between a mitotic block and commitment to terminal differentiation in the murine (Friend) erythroleukemia (FEL) cell. Since anticancer drugs are known to often block cell cycle transit typically in G2/mitosis, we tested a number of anticancer drugs with various modes of action and found that they all committed FEL cells to differentiate. Furthermore, other G2/mitosis-blocking drugs were also effective in inducing commitment. These results suggest (1) a causal relationship involving anticancer drugs, cell cycle block and differentiation, (2) that the search for new anticancer drugs utilize a differentiation assay and include G2/mitosis-blocking agents.
Dinnen
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RD
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Ebisuzaki
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001549:Benzamides; C025160:3-aminobenzamide; D004121:Dimethyl Sulfoxide