Interactions between white tea and sulindac in the prevention of intestinal cancer

4895

Non-steroidal anti-inflammatory drugs (NSAIDs) show considerable promise for prevention of intestinal cancer in humans. However, these drugs can produce severe toxicity, limiting their value as chemopreventive agents. One possible strategy to minimize side-effects of NSAIDs is to use lower doses in combination with other agents having complementary mechanisms. Teas are essentially non-toxic and are protective in many animal models of cancer. We previously demonstrated that a combination of white tea plus the conventional NSAID sulindac is highly effective at inhibiting tumor multiplicity in C57BL/6J-APCMin/+ (Min) mice. The current study was designed to determine if the interaction between tea and sulindac is independent (additive) or positive (synergistic). Each inhibitor was tested at multiple concentrations alone and in combination with the other agent. Tea was administered in the drinking water at concentrations producing 10 and 40 percent inhibition of tumor multiplicity (IC10 and IC40). Sulindac was given in the diet at the IC25, IC50, and IC75. The combination of white tea plus sulindac provided significantly greater inhibition of tumor multiplicity than sulindac alone for each of the combinations. For example, the combination of 40 ppm sulindac (IC25) plus 1.5% white tea (IC40) was comparable in effectiveness to 160 ppm sulindac. Using a model for examining independent interactions of chemopreventive agents, white tea and sulindac interact in a positive manner towards small intestinal tumor multiplicity with greatest interaction at the lower concentrations (Fig. 1). This research provides additional evidence that the combination of white tea plus sulindac is highly effective at inhibiting intestinal neoplasia in male Min mice. Administering these agents in combination may allow for lower, less toxic doses of sulindac to be as effective as higher doses (NIH-CA100608 and CA97485).