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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The crystal structure of the complex formed by bovine trypsin and Bowman-Birk type protease inhibitor AB-I extracted from azuki beans (Vigna angularis) 'Takara' has been analyzed. The structure was solved by the application of the phase combination of single isomorphous phases and trypsin model phases, followed by phase improvement using the iterative Fourier technique. From the resulting electron density map, a three-dimensional atomic model of the trypsin binding domain of AB-I has been built. The peptide chain at the trypsin reactive site turns back sharply at Pro29 and forms a 9-residue ring (Cys24-Cys32). The 'front side' of this ring, consisting of the reactive site (Cys24-Met28), interacts with trypsin in a similar manner to other families of inhibitors and forms a stable complex, which seems to be maintained by the interactions with the 'back side' of this ring (Pro29-Cys34). The similar spatial arrangements of the 'back side' of this inhibitor and the 'secondary contact region' of the other inhibitors with respect to the reactive site suggest an important common role of these regions in exhibiting inhibitory activity.

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Background. Epidemiologic and experimental studies suggest that dietary fish oil and vegetable oil high in ω‐3 polyunsaturated fatty acids (PUFAs) suppress the risk of colon cancer. The optimal amount to prevent colon carcinogenesis with perilla oil high in ω‐3 PUFA α‐linolenic acid in a 12% medium‐fat diet was investigated in female F344 rats. For comparison, safflower oil high in ω‐6 PUFA linoleic acid was used. Methods. Thirty or 25 rats at 7 weeks of age in each group received an intrarectal dose of 2 mg N‐methyl‐N‐nitrosourea 3 times weekly in weeks 1 and 2 and were fed the diets with various levels of perilla oil and safflower oil throughout the experiment. Results. The incidence of colon cancer at the termination of the experiment at week 35 was 40%, 48%, and 32% in the rats fed the diets with 3% perilla oil plus 9% safflower oil, 6% perilla oil plus 6% safflower oil, and 12% perilla oil plus 0% safflower oil, respectively, whereas it was 67% in the rats fed the control diet with 0% perilla oil plus 12% safflower oil. The amount of diet consumed and the body weight gain were identical in all of the dietary groups. The ratios of ω‐3 PUFA to ω‐6 PUFA in the serum and the colonic mucosa at week 35 were increased in parallel to the increased intake of perilla oil. Conclusions. The results suggest that a relatively small fraction of perilla oil, 25% of total dietary fat, may provide an appreciable beneficial effect in lowering the risk of colon cancer.