In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5713-5713
Abstract:
Omega-3 (n-3) fatty acids, especially the long-chain polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaonoic acid (DHA), have been shown to have potential antitumor effects for a wide range of cancer types, including breast. Multiple and widely diverse mechanisms have been purported through which n-3 fatty acids act as antitumor agents. Due to this wide range of effects, the n-3 fatty acids EPA and DHA in particular have been extrapolated to be possible chemo-preventive agents. Recent epidemiological studies have demonstrated that high intake of n-3 fatty acids from fish is inversely correlated with breast cancer risk. In this current study, we explore the molecular and cellular effects of EPA and DHA in breast cancer cells demonstrating abnormalities similar to those found in high risk patient populations, including MCF-7 cells with stable suppression of PTEN expression, MDA-MB-231 cells that mimic the triple negative phenotype and mouse epithelial cells that are derived from MMTV-erbB2 mouse breast tumors. Loss of PTEN activity has been reported in as much as 50% of all breast cancers. Triple negative disease exhibits an aggressive and early pattern of metastasis, with limited treatment options and a poor prognosis. ErbB2 is overexpressed in 30% of breast tumors and has been associated with a more aggressive and a pro-inflammatory disease. Based upon the highly inflammatory nature of these three cell types, we hypothesized that omega-3 fatty acids would be effective in modulating cellular processes that promote the more aggressive phenotype associated with these abnormalities. We are investigating the effect of EPA and DHA on survival, proliferation and apoptosis of the three modulated cell lines in comparison to less aggressive cell lines, and the molecular changes that correlate with response. Preliminary data suggest that cell proliferation is not modulated by exposure to either EPA or DHA. However, both EPA and DHA effectively suppressed NF-kB transcriptional activity in these cells. These data suggest that one important mechanism by which omega-3 fatty acids may function as anti-tumor and possibly chemo-preventive agents is through regulation of NF-kB-induced inflammation. Studies are currently on-going to evaluate if modulation of NF-kB is critical for mediating the protective effects of omega-3 fatty acids on breast cancer development and progression and if reduction of inflammatory responses will correlate with a less aggressive disease in these cells that closely reflect high risk patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5713.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-5713
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
