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Abstract
Pancreatic cancer BxPC-3 cells were exposed to curcumin, docosahexaenoic acid (DHA), or combinations of both and analyzed for proliferation and apoptosis. Pancreatic tumor xenografts were established by injecting BxPC-3 cells into each flank of nude mice. After the tumors reached a size of approximately 190–200 mm3, animals were fed diets with or without 2,000 ppm curcumin in 18% corn oil or 15% fish oil + 3% corn oil for 6 more wk before assessing the tumor volume and expression of inducible nitric oxide synthase (iNOS), cyclooxygeanse-2 (COX-2), 5-lipoxinase (5-LOX), and p21. A synergistic effect was observed on induction of apoptosis (approximately sixfold) and inhibition of cell proliferation (approximately 70%) when cells were treated with curcumin (5 μ M) together with the DHA (25 μ M). Mice fed fish oil and curcumin showed a significantly reduced tumor volume, 25% (P < 0.04) and 43% (P < 0.005), respectively, and importantly, a combination of curcumin and fish oil diet showed > 72% (P < 0.0001) tumor volume reduction. Expression and activity of iNOS, COX-2, and 5-LOX are downregulated, and p21 is upregulated in tumor xenograft fed curcumin combined with fish oil diet when compared to individual diets. The preceding results evidence for the first time that curcumin combined with omega-3 fatty acids provide synergistic pancreatic tumor inhibitory properties.
ACKNOWLEDGMENTS
We want to thank the technical staff of the Rodent Barrier Facility at the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Our thanks to Mr. Chang-In Choi for the help with the animal experiments as well as Ms. Alyson Atchison for help with the preparation of this manuscript. Also, we want to thank Omega Protein Inc., Houston, Texas, for generous supply of premium grade fish oil for the animal experiments. This work was in part supported by Kerley-Cade Chair Cancer Research Funding.
Notes
a Diet was formulated based on the American Institute of Nutrition Standard reference diet, with the modification of varying sources of carbohydrate (Citation38).