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.


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.


RESULTS
Aspirin at low, nontoxic concentrations induced differentiation leading to terminal cell division. Aspirin had no effect on PGE2 production and minimal inhibitory effect on COX activity. Furthermore, salicylate, a major metabolite of aspirin and an ineffective COX inhibitor, induced differentiation at concentrations comparable to aspirin. Similar experiments with MSM indicated that MSM had no effect on PGE2 production or on COX activity under differentiation--inducing conditions and at concentrations reported in other studies.


CONCLUSIONS
These experiments indicated that aspirin and MSM induced differentiation by a COX-independent mechanism(s) and suggested that a common mechanism for the chemopreventive action invoked by both agents might be the activation of gene functions leading to differentiation and thereby dismantling the cellular capacity for proliferation.
Ebisuzaki
Kaney
K
Departments of Microbiology and Immunology and of Biochemistry, University of Western Ontario, London, Ontario, N6A-5C1, Canada. kebisuza@julian.uwo.ca
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004121:Dimethyl Sulfoxide; D015232:Dinoprostone / Q000096:biosynthesis; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology; D051379:Mice; D013450:Sulfones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D016861:Cyclooxygenase Inhibitors; D013450:Sulfones; C025910:dimethyl sulfone; D015232:Dinoprostone; D001241:Aspirin; D004121:Dimethyl Sulfoxide