In an article published online on April 1, 2009 in the journal Cell Division, Egyptian researchers report that the omega-3 fatty acid docosahexaenoic acid (DHA), found in fish and the algae they consume, not only offers its own protection against tumor growth, but improves the chemotherapeutic effects of cisplatin while reducing its toxicity.
Professor A. M. El-Mowafy of Mansoura University’s Department of Biochemistry and associates administered 125 milligrams per kilogram (mg/kg) DHA, 250 mg/kg of DHA, cisplatin alone, cisplatin combined with 125 mg/kg DHA, or a control substance to groups of 8 to 10 mice implanted with mammary carcinoma cells. A group of mice not implanted with tumor cells served as controls. Serum C-reactive protein (CRP, a marker of inflammation), white blood cells, and MDA (a marker of lipid peroxidation) were measured, and tumor development was assessed after 20 days.
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.
"DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of cisplatin as well," Dr El-Mowafy commented. "Furthermore, this study is the first to reveal that DHA can obliterate lethal cisplatin-induced nephrotoxicity and renal tissue injury."
"The chemoprevention elicited by DHA was dose-dependent, and appeared to be mediated by reduction of leukocytosis, oxidative stress, and replenishing of endogenous antioxidant machinery," the authors write. "Most strikingly, a strong anti-inflammatory effect was produced that was highly reflected by reduction in CRP level. We provided novel, strong evidence that CRP serves as a sensitive diagnostic/prognostic marker both for tumor progression and responsiveness to chemotherapy in solid tumors."
"In essence, the renal protective and animal rescuing effects obtained for DHA, as well as its capacity to ameliorate leukocytosis, oxidant stress and inflammation, further substantiate its produced chemoprevention/chemo-enhancing profiles," they conclude. "This could, therefore, suggest a new fruitful drug regimen in the management of solid tumors based on combining cisplatin with DHA."