|Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Differences in the incidence and prognosis of breast cancer between Western women and Japanese or Eskimos (Greenland and Alaska) women may arise from contrasting patterns of dietary fat intake. Whereas the former group consumes high-fat diets containing n-6 polyunsaturated fatty acids (PUFAs), primary linoleic acid (LA), the latter group consumes large amounts of fat derived from fish oils containing n-3 PUFAs, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). An inverse relationship has been found between the incidence of breast cancer and the level of fish consumption, suggesting a protective role of n-3 PUFAs from human breast cancer. Thus, n-3 PUFAs have a potential role as chemopreventive and treatment agents in breast cancer. Therefore, we have studied the promotive or inhibitory effects of linoleic acid, EPA and DHA on breast cancer in vivo and in vitro.
(1) While linoleic acid promoted the growth and metastases of MM48 mammary tumor transplanted into mice, EPA and DHA inhibited them.
(2) In an in vitro study, linoleic acid stimulated the secretion of prostaglandin E and leukotriene B and cell growth of MDA-MB-231 human breast cancer. In contrary, EPA and DHA inhibited them, particularly at the EPA/n-6 ratio of 1 : 0.69 and the DHA/n-6 ratio of 1 : 2.08. Moreover, the cell growth was correlated with the prostaglandin level rather than the leukotriene level.
(3) In another in vitro study, linoleic acid stimulated the cell growth of MAD-MB-231 and MCF-7. Moreover, linoleic acid stimulated the c-myc expression in MCF-7.
Therefore, it was suggested that the promotive or inhibitory effects of linoleic acid, EPA and DHA are mediated via the arachidonic products or oncogen such as c-myc. However, their exact mechanisms still remained unclear and further studies are needed.