Docosahexaenoic acid intake decreases proliferation, increases apoptosis and decreases the invasive potential of the human breast carcinoma cell line MDA-MB-231

Abstract

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...

Suppression of PPARβ, and DHA treatment, inhibit NaV1.5 and NHE-1 pro-invasive activities

“…Our data showing that DHA treatment inhibits nNa V 1.5 current, and NHE-1 activity (and breast cancer cell invasiveness as reported by others [5,29]) agrees with, and extend, Isbilen et al (2006) published work showing that DHA inhibited nNa V 1.5 mRNA and protein expression [24]. However, we did not observe that cell migration was reduced by DHA.…”

“…1c). Dose-dependent analyses of DHA effects on MDA-MB-231 cells have previously been published [4,5,29] and doses ≤1 μM reduced Na V 1.5 expression [24], but not cell proliferation (n=11) (Fig. 1f).…”

“…A diet enriched in those n-3 PUFA increased survival and chemotherapy efficacy in breast cancer patients with severe metastatic disease [7]. In fact, supplementations of the diets or culture media with DHA were sufficient to reduce rodent mammary tumor growth [25], human breast cancer cell growth [4,42], cell migration [24], and invasiveness [5,29]. DHA is a natural ligand of peroxisome proliferator-activated receptors (PPAR) [17,30,41,45].…”

Docosahexaenoic acid inhibits the invasion of MDA-MB-231 breast cancer cells through upregulation of cytokeratin-1

“…However, few studies have also shown the inhibitory effect of DHa on the metastatic and invasive potential of cancer cells (9,27,28). in order to identify membrane proteins from MDa-MB-231 that could be involved, a 2-De-based proteomic analysis was performed with crude membrane preparations.…”

“…the mechanism by which DHa could prevent tumorigenesis or directly target cancer cells remains unclear (7). However, it has been shown that DHa not only acts as an anti-proliferative agent by lengthening the cell cycle between the G2/M transition (8), but also it is capable of inducing apoptosis and reducing the invasive potential of the triple-negative breast cancer cell line MDa-MB-231 with an optimal amount of 100 µM (9). DHa can modify the metastatic phenotype of cancer cells, emphasizing the anti-cancer potential of the omega-3 (n-3) Pufas (10,11).…”