Omega-3-Polyunsaturated Fatty Acids Suppress Pancreatic Cancer Cell Growth in vitro and in vivo via Downregulation of Wnt/Beta-Catenin Signaling

Abstract Background/Aims: ω3-polyunsaturated fatty acids (ω3-PUFAs) are known to possess anticancer properties. However, the relationship between ω3-PUFAs and β-catenin, one of the key components of the Wnt signaling pathway, in human pancreatic cancer remains poorly characterized. Methods: Human pa...

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Published in:Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2011-12, Vol.11 (6), p.574-584
Main Authors: Song, Kyoung-Sub, Jing, Kaipeng, Kim, Jong-Seok, Yun, Eun-Jin, Shin, Soyeon, Seo, Kang-Sik, Park, Ji-Hoon, Heo, Jun-Young, Kang, Jing X, Suh, Kwang-Sun, Wu, Tong, Park, Jong-Il, Kweon, Gi-Ryang, Yoon, Wan-Hee, Hwang, Byung-Doo, Lim, Kyu
Format: Article
Language:English
Subjects:
Adenocarcinoma - drug therapy
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Animals
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
catenin
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
desaturase
Docosahexaenoic acid
Docosahexaenoic Acids - pharmacology
Down-Regulation - drug effects
Drug Screening Assays, Antitumor
Eicosapentaenoic acid
Eicosapentaenoic Acid - pharmacology
Endocrinology & Metabolism
Fatty acids
Gastroenterology and Hepatology
Gene Expression Regulation, Neoplastic - drug effects
Humans
IAP protein
Lymphocytes T
Mice
Mice, Transgenic
Original Paper
Pancreatic cancer
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - pathology
Polyunsaturated fatty acids
Signal transduction
Transgenic mice
Tumors
Wnt protein
Wnt Signaling Pathway - drug effects
Wnt Signaling Pathway - genetics
Wnt/β-catenin
ω3-PUFAs
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Summary:Abstract Background/Aims: ω3-polyunsaturated fatty acids (ω3-PUFAs) are known to possess anticancer properties. However, the relationship between ω3-PUFAs and β-catenin, one of the key components of the Wnt signaling pathway, in human pancreatic cancer remains poorly characterized. Methods: Human pancreatic cancer cells (SW1990 and PANC-1) were exposed to two ω3-PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), to investigate the relationship between ω3-PUFAs and the Wnt/β-catenin signaling pathway in vitro. Mouse pancreatic cancer (PANC02) cells were implanted into fat -1 transgenic mice, which express ω3 desaturases and result in elevated levels of ω3-PUFAs endogenously. The tumor size, levels of Wnt/β-catenin signaling molecules and apoptosis levels were analyzed to examine the influence of ω3-PUFAs in vivo. Results: DHA and EPA significantly inhibited cell growth and increased cell death in pancreatic cancer cells. DHA also reduced β-catenin expression, T cell factor/lymphoid-enhancing factor reporter activity and induced β-catenin/Axin/GSK-3β complex formation, a known precursor to β-catenin degradation. Furthermore, Wnt3a, a natural canonical Wnt pathway ligand, reversed DHA-induced growth inhibition in PANC-1 cells. Immunohistochemical analysis showed aberrant upregulation and increased nuclear staining of β-catenin in tumor tissues from pancreatic cancer patients. However, β-catenin levels in tumor tissues from fat-1 transgenic mice were reduced with a significant increase in apoptosis compared with those from control mice. Conclusion: ω3-PUFAs may be an effective therapy for the chemoprevention and treatment of human pancreatic cancer.
ISSN:1424-3903
1424-3911
DOI:10.1159/000334468