Compositions for Treatment of Cancer and Inflammation
Pp. 465-480 (16)
Shahar Lev-Ari, Dov Lichtenberg and Nadir Arber
Celecoxib (Celebrex, Pfizer, NY, USA) is a worldwide top branded COX-2-specific inhibitor. It was shown to provide relief of arthritic pain and inflammation and has recently been under investigation for the prevention and treatment of cancer. However, recent studies showed that long term use of high doses of celecoxib is associated with an increased cardiovascular toxicity. We discovered that the addition of curcumin, a natural COX-2 inhibitor, to celecoxib synergistically (up to 1000%) augments the growth inhibitory effects of celecoxib in in vitro and in vivo models of arthritis and cancer, thus rendering effective action of the drug at up to tenfold lower dose. This may pave the way for a novel strategy to treat arthritis and cancer because its effect  can be achieved in the serum of patients receiving standard anti-inflammatory or anti-neoplastic dosages of celecoxib, and  involves a regimen with a very low profile of side effects. Preliminary data suggest that the combination is not limited only to celecoxib and that addition of curcumin to other NSAIDs such as sulindac, synergistically augments neoplastic cell growth inhibition. Based on these findings we received an IRB approval to evaluate celecoxib+curcumin in patients with osteoarthritis, pancreatic cancer and metastatic CRC. We hope to complete these novel human clinical trials, in 12-18 months.
Colorectal cancer, Curcumin, Celecoxib, COX-2, synergism
Department of Cancer Prevention, Tel Aviv Medical Center and The Sackler Faculty of Medicine, Tel Aviv University, Israel.