title: Docosahexaenoic acid inhibited the Wnt/β-catenin pathway and suppressed breast cancer cells in vitro and in vivo.
abstract: N-3 fatty acids (FAs) are essential FAs necessary for human health and are known to possess anticancer properties. However, the relationship between n-3 FAs and β-catenin, one of the key components of the Wnt signaling pathway, in mouse breast cancer remains poorly characterized. In this study, 4T1 mouse breast cancer cells were exposed to a representative n-3 FA, docosahexaenoic acid (DHA), to investigate the relationship between n-3 FAs and the Wnt/β-catenin signaling pathway in vivo and in vitro. In vitro studies showed that DHA strongly inhibited cell growth, and induced G1 cell cycle arrest both in 4T1 mouse breast cells and MCF-7 human breast cells. DHA reduced β-catenin expression and T cell factor/lymphoid-enhancing factor reporter activity in 4T1 mouse breast cells. In addition, DHA down-regulated the expression of downstream target genes such as c-myc and cyclinD1. In vivo, therapy experiments were conducted on Babl/c mice bearing breast cancer. We found that feeding mouse the 5% fish oil-supplemented diet for 30 days significantly reduced the growth of 4T1 mouse breast cancer in vivo through inhibition of cancer cell proliferation as well as induction of apoptosis. Feeding animals a 5% fish oil diet significantly induced down-regulation of β-catenin in tumor tissues with a notable increase in apoptosis. In addition, fish oil-supplemented diet decreased lung metastases of breast cancer. These observations suggested that DHA exerted its anticancer activity through down-regulation of Wnt/β-catenin signaling. Thus, our data call for further studies to assess the effectiveness of fish oil as a dietary supplement in the prevention and treatment of breast cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong Province, 266021, China. Electronic address: snowml@126.com.
authors.forename: Meilan
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao 266003, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Qingdao Center Medical Group, Shandong, China.
authors.forename: Jinglan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Center for Disease Control and Prevention, Qingdao, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong Province, 266021, China.
authors.forename: Yinlin
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong Province, 266021, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong Province, 266021, China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College, Qingdao University, Qingdao, Shandong Province, 266021, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D004281:Docosahexaenoic Acids
keywords: Breast cancer; Docosahexaenoic acid; Fish oil; Tumor-bearing mouse; Wnt signaling; β-catenin