Abstract. Breast cancer is the most common cancer in women in industrialized countries. Environmental factors, such as differences in diet are likely to have an important influence on cancer emergence. Among these factors, n-3 polyunsaturated-fatty acids, such as docosahexaenoic acid (DHA), are good candidates for preventing breast cancer. Here we investigate the effect of DHA on the human breast cancer cell line MDA-MB-231 and show that DHA incorporation i) has an anti-proliferative effect, ii) induces apoptosis via a transient increase in caspase-3 activity and the promotion of nuclear condensation, and iii) reduces the invasive potential of MDA-MB-231 cells. To conclude, DHA may have beneficial effects as a result of slowing the proliferation of tumor cells, and minimizing their metastatic potential.
IntroductionFor several decades, genetic and environmental factors have been explored in order to elucidate the appearance of tumors. Genetic factors are obviously involved in carcinogenesis, but diet is an environmental factor that is likely to have an influence on health (1), and particularly on tumor emergence (2-4). It has been shown that n-3 polyunsaturated, long-chain fatty acids (PUFAs), such as docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), are able to play an important preventive role in cardiovascular disease (5) and cancer (6). This conclusion is based partly on the observation that the incidence of these diseases is lower in Japanese people, whose diet is seafood based, resulting in a more balanced ratio between n-3 and n-6 PUFA than that of the Western diet (7). Even though this resource may be depleted in the future by the overharvesting of n-3 PUFA rich fish, it could be replaced by using marine microalgae, which have been identified as an important alternative source of DHA and EPA (8,9). Breast cancer is one of the cancers most frequently observed in industrialized countries, and the one with the highest incidence in women. Epidemiological studies have shown that the rate of breast cancer is 4 to 5 times higher in Western countries than in Japan (1,10). The mechanism by which DHA and EPA could provide protection against the appearance of a tumor, or directly influence cancer cells by reducing their malignancy, remains unclear, since cohort studies do not reveal any correlation between fat intake and breast cancer (1). Nevertheless, some evidence hints that DHA not only acts as an anti-proliferative agent by lengthening the cell cycle between the G2/M transition (11), but is also a proapoptotic factor, increasing caspase-3 and Bax (12,13). In addition, DHA has been shown to affect cell proliferation, whatever its source (i.e., fish oil or microalgae) (14). It has also been shown that the n-3 PUFAs and DHA, in particular, can act on lipid peroxidation as well as on the proteins implicated in the ROS mechanism leading to cell death (15,16).In this study, the effects of two concentrations of DHA (20 and 100 μM) were investigated on the human breast cancer cell line MDA-MB-231. DHA incorpo...