title: Naringin inhibits growth potential of human triple-negative breast cancer cells by targeting β-catenin signaling pathway.
abstract: Triple-negative (ER-/PR-/HER2-) breast cancer (TNBC) is a severe clinical problem because of its relatively poorer prognosis, aggressive behavior and lack of targeted therapies. Naringin, a major flavonoid extracted from citrus fruits, has been reported to exert promising anticancer activities. However, the detailed antitumor mechanism of naringin still remains enigmatic. In this study, TNBC cell lines-based in vitro and in vivo models were used to explore the anticancer effect and mechanism of naringin. Our data demonstrated that naringin inhibited cell proliferation, and promoted cell apoptosis and G1 cycle arrest, accompanied by increased p21 and decreased survivin. Meanwhile, β-catenin signaling pathway was found to be suppressed by naringin. In contrast, over-expressing β-catenin by adenoviral vector system in TNBC cells reversed the antitumor activity of naringin, and regulated p21 and survivin. Correspondingly, the antitumor potential of naringin was also observed in naringin-treated MDA-MB-231 xenograft mice, while immunohistochemical analysis of tumors from naringin-treated mice showed higher expression of p21 and lower expression of survivin and active β-catenin. Taken together, these results indicate that naringin could inhibit growth potential of TNBC cells by modulating β-catenin pathway, which suggests naringin might be used as a potential supplement for the prevention and treatment of breast cancer.
authors.affiliation: Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.
authors.forename: Hongzhong
authors.initials: H
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Tingxiu
authors.initials: T
authors.lastname: Xiang
authors.forename: Xuedong
authors.initials: X
authors.lastname: Yin
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
authors.forename: Fuling
authors.initials: F
authors.lastname: Luo
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Li
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D011897:Random Allocation; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C117749:Birc5 protein, mouse; D044950:Flavanones; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin; D051176:beta Catenin; C005274:naringin