Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids.
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 mm(3), 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 microM) together with the DHA (25 microM). 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.
Swamy
Malisetty V
MV
Department of Medicine, Hem-Onc Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Citineni
Bhargava
B
Patlolla
Jagan M R
JM
Mohammed
Altaf
A
Zhang
Yuting
Y
Rao
Chinthalapally V
CV
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005395:Fish Oils; D006801:Humans; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D023041:Xenograft Model Antitumor Assays
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D001094:Arachidonate 5-Lipoxygenase; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D003474:Curcumin