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British Journal of Cancer logoLink to British Journal of Cancer
. 1997;75(5):650–655. doi: 10.1038/bjc.1997.116

Inhibitory effects of docosahexaenoic acid on colon carcinoma 26 metastasis to the lung.

M Iigo 1, T Nakagawa 1, C Ishikawa 1, Y Iwahori 1, M Asamoto 1, K Yazawa 1, E Araki 1, H Tsuda 1
PMCID: PMC2063338  PMID: 9043019

Abstract

Unsaturated fatty acids, including n-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (C22:6, DHA) and eicosapentaenoic acid (C20:5, EPA), and a series of n-6 PUFAs were investigated for their anti-tumour and antimetastatic effects in a subcutaneous (s.c.) implanted highly metastatic colon carcinoma 26 (Co 26Lu) model. EPA and DHA exerted significant inhibitory effects on tumour growth at the implantation site and significantly decreased the numbers of lung metastatic nodules. Oleic acid also significantly inhibited lung metastatic nodules. Treatment with arachidonic acid showed a tendency for reduction in colonization. However, treatment with high doses of fatty acids, especially linoleic acid, increased the numbers of lung metastatic nodules. DHA and EPA only inhibited lung colonizations when administered together with the tumour cells, suggesting that their incorporation is necessary for an influence to be exerted. Chromatography confirmed that contents of fatty acids in both tumour tissues and plasma were indeed affected by the treatments. Tumour cells pretreated with fatty acids in vivo, in particular DHA, also showed a low potential for lung colony formation when transferred to new hosts. Thus, DHA treatment exerted marked antimetastatic activity associated with pronounced change in the fatty acid component of tumour cells. The results indicate that uptake of DHA into tumour cells results in altered tumour cell membrane characteristics and a decreased ability to metastasize.

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Selected References

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  1. Awad A. B., Spector A. A. Modification of the fatty acid composition of Ehrlich ascites tumor cell plasma membranes. Biochim Biophys Acta. 1976 Apr 5;426(4):723–731. doi: 10.1016/0005-2736(76)90137-1. [DOI] [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. Bertomeu M. C., Gallo S., Lauri D., Haas T. A., Orr F. W., Bastida E., Buchanan M. R. Interleukin 1-induced cancer cell/endothelial cell adhesion in vitro and its relationship to metastasis in vivo: role of vessel wall 13-HODE synthesis and integrin expression. Clin Exp Metastasis. 1993 May;11(3):243–250. doi: 10.1007/BF00121167. [DOI] [PubMed] [Google Scholar]
  4. Bégin M. E., Ells G., Das U. N., Horrobin D. F. Differential killing of human carcinoma cells supplemented with n-3 and n-6 polyunsaturated fatty acids. J Natl Cancer Inst. 1986 Nov;77(5):1053–1062. [PubMed] [Google Scholar]
  5. Cave W. T., Jr, Erickson-Lucas M. J. Effects of dietary lipids on lactogenic hormone receptor binding in rat mammary tumors. J Natl Cancer Inst. 1982 Feb;68(2):319–324. [PubMed] [Google Scholar]
  6. Cohen L. A., Thompson D. O., Choi K., Karmali R. A., Rose D. P. Dietary fat and mammary cancer. II. Modulation of serum and tumor lipid composition and tumor prostaglandins by different dietary fats: association with tumor incidence patterns. J Natl Cancer Inst. 1986 Jul;77(1):43–51. [PubMed] [Google Scholar]
  7. Corey E. J., Shih C., Cashman J. R. Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3581–3584. doi: 10.1073/pnas.80.12.3581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dahiya R., Boyle B., Goldberg B. C., Yoon W. H., Konety B., Chen K., Yen T. S., Blumenfeld W., Narayan P. Metastasis-associated alterations in phospholipids and fatty acids of human prostatic adenocarcinoma cell lines. Biochem Cell Biol. 1992 Jul;70(7):548–554. doi: 10.1139/o92-085. [DOI] [PubMed] [Google Scholar]
  9. Dustin L. B., Shea C. M., Soberman R. J., Lu C. Y. Docosahexaenoic acid, a constituent of rodent fetal serum and fish oil diets, inhibits acquisition of macrophage tumoricidal function. J Immunol. 1990 Jun 15;144(12):4888–4897. [PubMed] [Google Scholar]
  10. Falconer J. S., Ross J. A., Fearon K. C., Hawkins R. A., O'Riordain M. G., Carter D. C. Effect of eicosapentaenoic acid and other fatty acids on the growth in vitro of human pancreatic cancer cell lines. Br J Cancer. 1994 May;69(5):826–832. doi: 10.1038/bjc.1994.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fulton A. M., Heppner G. H. Relationships of prostaglandin E and natural killer sensitivity to metastatic potential in murine mammary adenocarcinomas. Cancer Res. 1985 Oct;45(10):4779–4784. [PubMed] [Google Scholar]
  12. Ginsberg B. H., Jabour J., Spector A. A. Effect of alterations in membrane lipid unsaturation on the properties of the insulin receptor of Ehrlich ascites cells. Biochim Biophys Acta. 1982 Sep 9;690(2):157–164. doi: 10.1016/0005-2736(82)90318-2. [DOI] [PubMed] [Google Scholar]
  13. Gupta C. The role of prostaglandins in masculine differentiation: modulation of prostaglandin levels in the differentiating genital tract of the fetal mouse. Endocrinology. 1989 Jan;124(1):129–133. doi: 10.1210/endo-124-1-129. [DOI] [PubMed] [Google Scholar]
  14. Iigo M., Tsuda H., Moriyama M. Enhanced therapeutic effects of anti-tumour agents against growth and metastasis of colon carcinoma 26 when given in combination with interferon and interleukin-2. Clin Exp Metastasis. 1994 Nov;12(6):368–374. doi: 10.1007/BF01755880. [DOI] [PubMed] [Google Scholar]
  15. Kier A. B., Franklin C. Membranes of high- and low-metastatic L tumor cell variants. Invasion Metastasis. 1991;11(1):25–37. [PubMed] [Google Scholar]
  16. Raz A., Ben-Ze'ev A. Cell-contact and -architecture of malignant cells and their relationship to metastasis. Cancer Metastasis Rev. 1987;6(1):3–21. doi: 10.1007/BF00047606. [DOI] [PubMed] [Google Scholar]
  17. Rose D. P., Connolly J. M. Effects of dietary omega-3 fatty acids on human breast cancer growth and metastases in nude mice. J Natl Cancer Inst. 1993 Nov 3;85(21):1743–1747. doi: 10.1093/jnci/85.21.1743. [DOI] [PubMed] [Google Scholar]
  18. Rose D. P., Hatala M. A., Connolly J. M., Rayburn J. Effect of diets containing different levels of linoleic acid on human breast cancer growth and lung metastasis in nude mice. Cancer Res. 1993 Oct 1;53(19):4686–4690. [PubMed] [Google Scholar]
  19. Rose D. P., Hatala M. A. Dietary fatty acids and breast cancer invasion and metastasis. Nutr Cancer. 1994;21(2):103–111. doi: 10.1080/01635589409514309. [DOI] [PubMed] [Google Scholar]
  20. Schroeder F. Fluorescence probes in metastatic B16 melanoma membranes. Biochim Biophys Acta. 1984 Oct 3;776(2):299–312. doi: 10.1016/0005-2736(84)90219-0. [DOI] [PubMed] [Google Scholar]
  21. Taraboletti G., Perin L., Bottazzi B., Mantovani A., Giavazzi R., Salmona M. Membrane fluidity affects tumor-cell motility, invasion and lung-colonizing potential. Int J Cancer. 1989 Oct 15;44(4):707–713. doi: 10.1002/ijc.2910440426. [DOI] [PubMed] [Google Scholar]
  22. Wicha M. S., Liotta L. A., Kidwell W. R. Effects of free fatty acids on the growth of normal and neoplastic rat mammary epithelial cells. Cancer Res. 1979 Feb;39(2 Pt 1):426–435. [PubMed] [Google Scholar]

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