Our lab studies the inhibition of eicosanoid synthesis as means to decrease tumor growth and tumor angiogenesis. The research in our lab focuses on in vivo studies in mice, discovering and investigating cellular signaling mechanisms that are regulated by NSAIDs and other eicosanoids inhibitors. A key element in these studies is to determine whether or not these effects are due to the eicosanoid inhibiting properties of the specific drug or agent. The specific projects currently being investigated include:
- Characterization of the effects of chiral (asymmetric) NSAIDs (COX-inhibiting S-NSAID vs. non-inhibiting R-NSAID) on tumor growth and cell cycle parameters in vivo.
- Characterization of the anti-tumorigenic mechanisms of action of NSAIDs that do not inhibit either of the COX enzymes. Emphasis is on searching for novel non-COX mechanisms that nevertheless lead to attenuation of prostanoids formation.
- Demonstration of an unequivocal anti-carcinogenic action of lipoxygenase inhibitors in vivo and characterization of the molecular/cellular basis for this effect.
- Evaluation of in vivo inhibitors of inducible Nitric Oxide Synthase (NOS) as adjunctive cancer therapy agents for use in conjunction with COX inhibitors. 5. Evaluation in vivo of the cholesterol-lowering, HMG-CoA Reductase inhibitors (Lovastatin and other statins) as adjunctive cancer therapy agents for use together with COX inhibitors.
A second branch of our research effort focuses on dietary remodeling of cellular fatty acids in such a way as to substantially reduce arachidonic acid content and increase the content of long chain -3 fatty acids EPA and DHA. We (and others) have shown that such a change leads to a significant attenuation of tumor growth in experimental models in rodents. In full agreement with this, data from recent human epidemiological studies showed an inverse relationship between consumption of fish or fish oil (rich source of the w-3 fatty acids) and the prevalence of prostate cancer in men and breast cancer in women.
