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

Abstract

Summary Unsaturated fatty acids, including n-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (C225, 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.Keywords: docosahexaenoic acid; unsaturated fatty acid; metastasis; colon carcinoma 26As tumour metastasis exerts an adverse influence on the prognosis of patients and is a major cause of cancer death, a considerable number of investigations into its biological, molecular and genetic features have been conducted (Raz and Ben-Ze'ev, 1987; Bertomeu et al, 1993). These investigations have indicated that tumour metastases are established by an inter-related sequence of processes, depending on various factors derived from both the tumour and the host. There is substantial evidence that the membrane properties of tumour cells play a major role in the interactions between themselves and the surrounding environment (Awad and Spector, 1976;Schroeder, 1984;Taraboletti et al, 1989;Dahiya et al, 1992). Studies on mice have revealed that plasma membranes of tumour sublines with high metastatic ability exhibit a more fluid state than those with low metastatic ability, based on differences in lipid composition and lipid-protein ratios (Kier and Franklin, 1991). Furthermore, studies have demonstrated that the chemical and physical properties of cell membranes are modified by both the amount and type of fat in the diet, and this influences growth and/or alters the metastatic ability of tumour cells (Chen et al, 1992;Rose and Hatala, 1994). Diets rich in linoleic acid have been found to enhance the growth and metastasis of transplantable mammary carcinomas in rodents (Rao and Abraham, 1976;. In a study of dietary n-3 PUFAs in a ...

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