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More Evidence That Fish Oil Inhibits Breast Cancer
9/5/2005
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Study in mice and test tubes illuminates how fish-derived omega-3s undermine breast cancer

by Craig Weatherby



Last October we reported the groundbreaking results of a study that looked at relationships between dietary fat and risk of breast cancer.  Researchers at the University of Southern California examined data from the Singapore Chinese Health study, and found that women who consumed high levels of dietary omega-3s from fish and shellfish were at significantly lower risk of getting breast cancer (see “Omega-3s and fish seen to reduce breast cancer risk”).


Now, the results of a study published on the Web site of the International Journal of Cancer may help cancer researchers understand some of the means by which omega-3s from fish seem to retard the growth of malignant breast tumors.


Researchers from Indiana University, Purdue University, and Indiana’s Methodist Research Institute implanted mice with cultured breast cancer cells, and fed the animals either fish oil high in marine omega-3 fatty acids (EPA and DHA) or corn oil high in omega-6 fatty acids.


Just three weeks after implantation of tumors, the volume and weight of the malignancies were significantly lower in the mice on the fish oil diet, compared to the tumors in mice on the corn oil diet.  And, inhibition of tumor growth increased with the amount of fish oil that mice consumed.


The researchers also performed a parallel test tube experiment on breast cancer cells exposed to either fish-derived omega-3s or omega-6s from corn oil.  The results showed that marine omega-3s inhibited tumor cell growth by about 23 percent, while corn oil had no effect.


Omega-3s cause cancer to commit suicide

These experiments were especially valuable because they showed that the marine omega-3s in fish oil fight breast cancer by raising levels of an enzyme called N-SMYase (neutral sphingomyelinase) by 40 percent. This enzyme promotes apoptosis, or spontaneous cancer cell death.  As proof, spontaneous cancer-cell death dropped by 40 percent when the researchers introduced a chemical (GW4869) that blocks N-SMYase.


In addition to increased levels of this key anti-cancer enzyme, three other anti-cancer effects were seen in the mice fed omega-3s, and/or in the cancer cells exposed to marine omega-3s:

  • Omega-3s produced an increase in levels of ceramide, a chemical that is a common intermediate step in many metabolic pathways leading toward spontaneous cancer-cell death.
  • Omega-3s increased formation of protrusions called blebs on the membranes of the cancer cells: an event associated with spontaneous death of cancer cells.
  • Omega-3s induced greater expression of p21: a gene that facilitates repair of cellular DNA and can inhibit proliferation of cancer cells (Note: In some circumstances, p21 can help cancer cells survive, but in this case, the several other anti-cancer effects of omega-3s appear to overwhelm any such possible effect).

While these findings in mice and cultured cancer cells do not prove that diets high in fish or fish oil can prevent or cure breast cancer, they provide a biochemical rationale for the significantly reduced risk of breast cancer seen in the landmark Singapore health study.



Sources

  • Wu M, Harvey KA, Ruzmetov N, Welch ZR, Sech L, Jackson K, Stillwell W, Zaloga GP, Siddiqui RA. Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway. Int J Cancer. 2005 May 17; [Epub ahead of print]
  • Gago-Dominguez M, Yuan JM, Sun CL, Lee HP, Yu MC. Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study. Br J Cancer. 2003 Nov 3;89(9):1686-92.
  • Chen HW, Chiang T, Wang CY, Lii CK. Inhibition of tert-butyl hydroperoxide-induced cell membrane bleb formation by alpha-tocopherol and glutathione. Food Chem Toxicol. 2000 Dec;38(12):1089-96.
  • Winters ZE, Leek RD, Bradburn MJ, Norbury CJ, Harris AL. Cytoplasmic p21WAF1/CIP1 expression is correlated with HER-2/ neu in breast cancer and is an independent predictor of prognosis. Breast Cancer Res. 2003;5(6):R242-9. Epub 2003 Oct 3.
  • Clark MA, Perks CM, Winters ZE, Holly JM. DNA damage uncouples the mitogenic response to IGF-I in MCF-7 malignant breast cancer cells by switching the roles of PI3 kinase and p21WAF1/Cip1. Int J Cancer. 2005 Sep 10;116(4):506-13.
  • Mukherjee S, Conrad SE. c-Myc suppresses p21WAF1/CIP1 expression during estrogen signaling and antiestrogen resistance in human breast cancer cells. J Biol Chem. 2005

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