Combination regimen of COX-2 inhibitor and fish oil causes cell death
Philadelphia, PA — A combination of low-dose COX (cyclooxygenase)-2 inhibitors (celecoxib) and a biologically active component of fish oil (n-3 PUFAs, such as docosahexanoic acid, DHA) may prevent, and even treat, colon cancer, according to data published in the Proceedings for the 94th Annual Meeting of the American Association for Cancer Research (AACR). This effect of the low-dose combination regimen on human colon cancer cells was more pronounced than the use of each agent separately at high doses.
“Any medications taken at high doses may be accompanied by negative side effects, which may make them undesirable for the prevention and treatment of cancer,” according to C.V. Rao, Ph.D., Associate Chief, Division of Nutritional Carcinogenesis, Institute For Cancer Prevention, American Health Foundation-Cancer Center, Valhalla, New York. “Therefore, we were pleased to see in our study that the combination treatment of COX-2 and fish oil component (DHA) was effective at tolerable doses.”
In the study, human colon cancer cells were treated with several concentrations of celecoxib in combination with DHA, and either celecoxib or DHA alone. The study measured markers including cell growth, cell death, COX-2 expression and activity, and iNOS (inducible nitric oxide synthesis) expression. Results showed that celecoxib and/ or DHA inhibit cell growth and induce cell death at concentrations of >100 ƒÝM
(micrometer) celecoxib and >150 ƒÝM DHA in the human colon cancer cell line HCA-7. However, combining low-dose levels of celecoxib (50 ƒÝM) and DHA (75 ƒÝM) results in synergistic suppression of cell growth and also induces cell death in HCA-7 cells. Importantly, the key molecular targets of celecoxib and DHA, COX-2 expression and activity, are also synergistically suppressed by low-dose combinations of these agents.
Previous pre-clinical (animal) studies have demonstrated that the administration of fish oil alone reduces the risk of colon cancer by 60 to 70 percent.
Subsequent animal studies compared effects of 20 percent of the fat types in a typical American diet with those of 20 percent levels of fish oil (high in omega 3 fatty acids), and found that the animals treated with fish oil developed 70 to 80 percent fewer tumors. It is noteworthy that even with a brief exposure to a fish oil diet, there was a significant suppression of precursor lesions of colon cancer. Similarly, COX-2 inhibitors have demonstrated reduction of colon cancer tumors by up to 30 percent in human clinical trials. COX-2 — an inducible enzyme generating prostaglandins (PG) — may be implicated in several biological events throughout the process of tumor development and is therefore a potential target for preventing and possibly treating a number of cancers.
Colorectal cancer is the third leading cause of death in both men and women. According the American Cancer Society, in 2003 more than 72,000 men and 74,000 women will be diagnosed with colorectal cancer, and more than 28,000 men and 28,000 women will die from the disease. Incidence rates have recently begun to stabilize, and death rates have actually declined for both and women over the past 15 years.
Founded in 1907, the American Association for Cancer Research (AACR) is a professional society of more than 20,000 laboratory and clinical scientists engaged in cancer research in the United States and more than 60 other countries. AACR’s mission is to accelerate the prevention and cure of cancer through research, education, communication and advocacy. Its principal activities include the publication of five major peer-reviewed scientific journals (Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention). AACR’s annual meeting attracts more than 12,000 participants who share new and significant discoveries in the cancer field, and the AACR’s specialty meetings throughout the year focus on all the important areas of basic, translational and clinical cancer research.