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.