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Impact of palmitic acid and α‐linolenic acid on the β‐catenin pathway with inhibition of the peroxisome proliferator‐activated receptor γ (PPARγ) in HCT116 colon cancer cells
Author(s) -
Myers Megan C,
Wetmore Lori
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.714.4
Subject(s) - palmitic acid , wnt signaling pathway , apoptosis , cancer research , colorectal cancer , chemistry , fatty acid , cancer , endocrinology , medicine , biology , biochemistry , signal transduction
Colon cancer arises when homeostasis of essential cell functions such as proliferation and differentiation is lost (Panza, 2013). Colon cancer cell function can be regulated by diet and/or the Wnt/β‐catenin pathway (Kim J, 2000; Kim YS, 2007). Some researchers speculate that activation of PPARγ, especially by certain fatty acids, can promote tumor development in the colon (Alex, 2013; Lefebvre, 1998) and that high levels of β‐catenin, influenced by PPARγ activation (Panza, 2013), is associated with increased risk of colon cancer (Earswaran, 1999). In cancerous cells, oxidative stress signals trigger cell cycle arrest and apoptosis (Storz, 2011), however cancerous cells have also been known to have increased levels of reactive oxygen species (ROS) as well (Korswagen 2006). The proposed research will elucidate the mechanism connecting fatty acids to colon cancer promotion/suppression via the Wnt/β‐catenin pathway and the relationship between fatty acid intake and ROS in colon cancer cells. We hypothesize first that palmitic acid, a saturated fatty acid, will increase expression of β‐catenin and α‐linolenic acid, an ω‐3 PUFA, will decrease expression of β‐catenin in HCT116 colon cancer cell. Secondly, we hypothesize that fatty acid activation of PPARγ will increase ROS production in HCT116 colon cancer cells. We used flow cytometry to analyze cell cycle progression of HCT116 cells when treated with fatty acids for 24 hours. HCT116 cells treated with fatty acids displayed the following average % cell population of sub‐G1 cells: control, 6.85±0.85; 0.5 mM Palmitic acid, 8.15±0.59; 0.5 mM linoleic acid, 4.49±0.22 and combined 0.5 mM palmitic acid + 0.5 mM linoleic acid, 27.63±24.76. Decreased G1 populations were noted in cells displaying increased sub‐G1 populations. This may indicate increased ROS production in cells treated with saturated palmitic acid. Analysis of β‐catenin expression and ROS production is currently underway. Support or Funding Information This study is funded by Beta Beta Beta National Biological Honor Society and the William Jewell College Biology and Chemistry Departments 1Proposed pathway of saturated fatty acid impact on β‐catenin when PPARγ is inhibited. Saturated fatty acids should increase β‐catenin levels, leading to increased tumorigenesis.2Mean percentage of cell cycle populations for HCT116 cells exposed to ethanol control, 0.5 mM palmitic acid,0.5 mM α‐linoleic acid, and a combination of the two fatty acids (0.5 mM palmitic acid + 0.5 mM α‐linoleic acid). Error Bars represent the standard error of the mean (n = 2).3Representative HCT 116 cell cycle histograms (FL2: 585±40nm) illustrating cell populations after 24‐hour exposure to A: 0.5 mM α‐linoleic acid, B: 0.5 mM palmitic acid, and C: combined 0.5 mM palmitic acid and 0.5 mM α‐linoleic acid, relative to 0.8% (v/v) ethanol control (gray filled).