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The combination effects index (CI) analysis confirmed the synergy of clioquinol and clofibrate on inhibiting cancer cell viability. Using inhibitors to block PPARalpha signaling diminished the synergistic cytotoxicity of clioquinol and DHA. These results provide pharmacological evidence that the synergistic anticancer action of clioquinol and DHA is mediated by PPARalpha signaling in human cancer cells. PPARalpha signaling mediates the synergistic cytotoxicity of clioquinol and docosahexaenoic acid in human cancer cells. Tuller ER, Brock AL, Yu H, Lou JR, Benbrook DM, Ding WQ. Biochem Pharmacol. 2009 May 1;77(9):1480-6. Epub 2009 Feb 13. PMID: 19426685

Simultaneously targeting epidermal growth factor receptor tyrosine kinase and cyclooxygenase-2, an efficient approach to inhibition of squamous cell carcinoma of the head and neck. Chen Z, Zhang X, Li M, Wang Z, Wieand HS, Grandis JR, Shin DM. Clin Cancer Res. 2004 Sep 1;10(17):5930-9. PMID: 15355926

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. Prevention and treatment of pancreatic cancer by curcumin in combination with omega-3 fatty acids. Swamy MV, Citineni B, Patlolla JM, Mohammed A, Zhang Y, Rao CV. Nutr Cancer. 2008;60 Suppl 1:81-9. PMID: 19003584

Mice injected with cancer cells experienced significantly elevated levels of C-reactive protein, white blood cells, and lipid peroxidation compared with control mice. These levels were reduced in animals that received cisplatin and/or DHA. While treatment with 125 mg/kg DHA inhibited tumor growth by 38 percent compared to untreated animals, 250 mg/kg suppressed tumor growth by 79 percent, which was a greater effect than that of cisplatin alone (which was associated with a 55 percent reduction). The combination of DHA and cisplatin resulted in an 81 percent inhibition of growth, while reducing elevated white blood cell levels (leukocytosis) to normal levels. Treatment with the higher dose of DHA alone was associated with a similar reduction in white blood cells, which, when elevated, are associated with tumor growth. A strong relationship was observed between tumor growth and white blood cell levels as well as C-reactive protein levels. In another experiment with rats treated with cisplatin, the addition of 250 mg/kg DHA prevented lethal kidney toxicity in 88 percent of the animals that received it, while none of the rats that received cisplatin alone survived.

Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides. Elmesery ME, Algayyar MM, Salem HA, Darweish MM, El-Mowafy AM. Cell Div. 2009 Apr 2;4(1):6. [Epub ahead of print] PMID: 19341447 doi:10.1186/1747-1028-4-6

ScienceDaily (Apr. 5, 2009) - Docosahexanoic acid (DHA), an omega-3 fatty acid found in fish oils, has been shown to reduce the size of tumours and enhance the positive effects of the chemotherapy drug cisplatin, while limiting its harmful side effects. The rat experiments provide some support for the plethora of health benefits often ascribed to omega-3 acids.