Selective preservation of protein kinase C-zeta in the chemoprevention of azoxymethane-induced colonic tumors by piroxicam.

While nonsteroidal anti-inflammatory drugs have been shown to exert preventive effects against the development of colonic tumors in humans and in chemically-induced tumors in animal models, the mechanism(s) involved in this phenomenon is unclear. We have recently demonstrated that one such agent, piroxicam, when supplemented (75 ppm) in the diets of rats administered azoxymethane, reduced the incidence of rats bearing tumors. To date, the effects of piroxicam on protein kinase C, a family of serine/threonine kinases which may be intimately involved in the colonic malignant transformation process, have not been examined. It was, therefore, of interest to determine whether piroxicam altered the expression of one or more isoforms of this kinase in these tumors. The present studies demonstrate that dietary piroxicam selectively preserved the expression of protein kinase C-zeta in azoxymethane-induced tumors; suggesting that this is at least one mechanism involved in this agent's chemopreventive actions in this organ.