Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice

Abstract

BackgroundSupplementing mice with high levels of dietary n-3 polyunsaturated fatty acids (PUFAs) increases the n-3 PUFAs in cell membranes, increases the susceptibility of the cells for lipid peroxidation (LPO) and decreases the growth rate of mammary and other tumors. However, the results of an earlier study indicated that a factor in addition to LPO was involved in the reduction in tumor growth in n-3 PUFAs fed mice. Athymic mice bearing MDA-MB-231 human breast carcinoma xenografts, were fed fish oil concentrate (FOC) or control diets, with and without supplemental Vitamin E (2000 IU /kg diet) and were sacrificed both before and after doxorubicin (DOX) treatment to evaluate factors involved in tumor growth suppression.ResultsPrior to DOX, basal LPO in the tumor of 3% FOC fed mice was slightly higher than in the control fed mice and was decreased in mice consuming FOC with vitamin E. Vitamin E suppressed the DOX induced increase in LPO in the tumors of control mice, however, vitamin E was not sufficient to suppress a DOX induced increase in LPO in the tumors of FOC fed mice. The mean growth rate of tumors of FOC fed mice was significantly less than the mean growth rate of the tumors of control mice. Multiple regression analyses indicated that suppression of glutathione peroxidase (GPX) activity by FOC prior to DOX therapy was more important than increased LPO as an explanation of tumor growth suppression. Tumor induced cachexia was decreased in mice consuming FOC.ConclusionsIt appears that the increased sensitivity to DOX was related to an FOC induced reduction in GPX activity. FOC reduced tumor induced cachexia.

Characterization of docosahexaenoic acid (DHA)-induced heme oxygenase-1 (HO-1) expression in human cancer cells: the importance of enhanced BTB and CNC homology 1 (Bach1) degradation

“…Among the cellular mechanisms described, DHA-induced lipid peroxidation has been well recognized to mediate DHA’s anticancer activity. Upon incorporation of DHA into tumor cell membranes, their susceptibility to lipid peroxidation is increased [10] and accumulation of the lipid peroxidation by-products causes peroxidative damage, ultimately leading to cell death [11]. These observations are further supported by the fact that the killing of malignant cells by DHA can be accelerated by increased cellular oxidative stress [12].…”

Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling

“…TAM has beneficial effects on some aspects of fatty acid metabolism, for example, by reducing cholesterol levels (Reckless et al, 1997). Diets containing n-3 PUFAs can increase the efficacy of cytotoxic drugs against ERÀ human breast cancer xenografts (MDA-MB-231) (Hardman et al, 2001). A recent study suggests that n-3 PUFAs restore TAM's ability to inhibit cell growth (DeGraffenried et al, 2003).…”

Closely related colon cancer cell lines display different sensitivity to polyunsaturated fatty acids, accumulate different lipid classes and downregulate sterol regulatory element‐binding protein 1

“…Epidemiological studies indicate that there is an inverse association between intake of polyunsaturated fatty acids (PUFAs) and incidence of breast, colon and prostate cancers, although these studies are not uniformly conclusive [1–4]. Also, cancer xenografts in immunosuppressed mice as well as cell culture studies demonstrate that PUFAs may slow down cancer cell growth, induce apoptosis and increase the efficiency of chemotherapeutic drugs [5–8]. The mechanisms behind these effects are clearly complex and not well understood.…”