In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 4207-4207
Abstract:
Excess levels of omega-6 fatty acids, commonly consumed in Western diets, are heavily implicated in contributing to prostate cancer incidence and tumor cell proliferation. Omega-6 fatty acids may promote worse outcome through the chronic production of eicosanoids that promote inflammation and oxidative stress. As omega-3 fatty acids competitively interact with some of the same rate-limiting enzymes to diminish inflammation and oxidative stress, epidemiologic studies have sought to determine if diets high in omega-3 fatty acids may impart beneficial effects on prostate cancer rates and progression. Pre-clinical observations indicate that omega-3 fatty acids suppress prostate tumor cell growth and induce cancer cell death, supporting a beneficial role of omega-3 fatty acids in delaying time to PSA failure and reducing the aggressiveness of advanced prostate cancer. As omega-3 fatty acids possess known pro-oxidant and antioxidant properties, we investigated the effects of docosahexaenoic acid (DHA-22:6n-3) in modulating oxidative DNA damage in normal and prostate cancer cells. Preliminary data demonstrates that prostate cancer cells (LNCaP) pretreated with DHA and pulsed with physiologic levels of H2O2 encounter a sustained G2 checkpoint arrest and exhibit decreased colony formation potential when compared to normal prostate epithelial cells (PrEC). LNCaP cells pulsed with 32 uM H2O2 exhibit DNA breaks associated with translocation of NF-κB into the nucleus, whereas pretreatment with DHA precluded NF-κB translocation, selectively sensitizing LNCaP cells, but not PrEC, to cell death. Further, DHA suppresses degradation of the NF-κB inhibitor, IκB, and attenuates NF-κB transcriptional activity as well as expression of the NF-κB downstream target, survivin. To conclusively demonstrate the critical role of NF-kB signaling in LNCaP cells after exposure to H2O2, we induced a 50% knockdown of p65 by siRNA and observe a complete ablation of colony formation relative to scrambled siRNA control vector. Here we describe one potential mechanism by which DHA may selectively increase genotoxicity in prostate cancer cells after exposure to oxidizing agents, ultimately setting the stage for Phase II clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4207. doi:10.1158/1538-7445.AM2011-4207
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-4207
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
