Aspirin and methylsulfonylmethane (MSM): a search for common mechanisms, with implications for cancer prevention.

Background: Aspirin (acetylsalicylic acid), a prototypic nonsteroidal anti-inflammatory drug (NSAID), and MSM, a "nutritional supplement", are both used in the treatment of arthritis and described as cancer chemopreventive agents. Initial experimentation indicating that aspirin and MSM also induced the differentiation of murine erythroleukemia (MEL) cells led to a search for common mechanisms involving these two agents.

Materials And Methods: Since the major mechanism of action attributed to aspirin is the inhibition of cyclooxygenase (COX), prostaglandin (PG) production was examined under differentiation-inducing conditions in MEL cells.

The search for novel anticancer agents: a differentiation-based assay and analysis of a folklore product.

One alternative approach to the current use of cytotoxic anticancer drugs involves the use of differentiation-inducing agents. However, a wider application of this strategy would require the development of assays to search for new differentiation-inducing agents. In this report we describe an in vitro assay using the murine erythroleukemia (clone 3-1) cells.

An endogenous signal triggering erythroid differentiation: identification as thyroid hormone.

The identification of thyroid hormone as an endogenous signal for erythroid differentiation began with our studies on the spontaneously differentiating murine erythroleukemia clone 3-1. We observed that the spontaneous differentiation frequency was dependent on a heat stable factor present in fetal calf serum or calf bone marrow. We also noted that the bone marrow extract stimulated erythroid colony-forming units in mouse bone marrow cells, suggesting the relevance of this factor in normal erythroid differentiation.

An anticancer drug-sensitive murine erythroleukemia clone: implications for the mechanism of action of antineoplastic drugs.

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.

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.