title: Selenium-enriched polysaccharides from Pyracantha fortuneana (Se-PFPs) inhibit the growth and invasive potential of ovarian cancer cells through inhibiting β-catenin signaling.
abstract: Polysaccharides from medicinal plants exert antitumor activity in many cancers. Our previous study demonstrated that polysaccharides extracted from the selenium-enriched Pyracantha fortuneana (Se-PFPs) showed antiproliferative effect in breast cancer cell line. This study aimed to investigate the antitumor effect of Se-PFPs in ovarian cancer cells in vitro and in vivo. Se-PFPs could decrease cell viability, induce apoptosis, and inhibit migratory and invasive potentials in HEY and SKOV3 cells. These findings are supported by reduced expression of cyclin D1, Bcl-2 and MMP-9, enhanced cleavage of PARP and caspase-3, elevated activity of caspase-3 and caspase-9, and EMT (epithelial to mesenchymal transition) inhibition (elevated expression of E-cadherin and cytokeratin 19, and reduced expression of N-cadherin, vimentin, ZEB1 and ZEB2). Moreover, Se-PFPs inhibited xenografted tumor growth through inhibiting cell proliferation and inducing cell apoptosis. More importantly, Se-PFPs significantly reduced cytoplasmic β-catenin particularly nuclear β-catenin expression but increased β-catenin phosphorylation in a GSK-3β-dependent mechanism. Furthermore, β-catenin knockdown exerted similar effects on cell proliferation and invasion as seen in Se-PFPs-treated cells, while β-catenin overexpression neutralized the inhibitory effects of Se-PFPs on cell proliferation and invasion. Take together,Se-PFPs exert antitumor activity through inhibiting cell proliferation, migration, invasion and EMT, and inducing cell apoptosis. These effects are achieved by the inhibition of β-catenin signaling. Thus Se-PFPs can be used as potential therapeutic agents in the prevention and treatment of ovarian cancer.
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China.
authors.forename: Qianling
authors.initials: Q
authors.lastname: Sun
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Dong
authors.affiliation: Renhe Hospital of China Three Gorges University, Yichang, HuBei 443002, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Molecular Medicine & Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Changdong
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China.
authors.forename: Deqiao
authors.initials: D
authors.lastname: Sheng
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Hubei Institute for Nationalities, Enshi, HuBei 445000, China.
authors.forename: Debin
authors.initials: D
authors.lastname: Huang
authors.affiliation: College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China.
authors.forename: Chengfu
authors.initials: C
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D031991:Pyracantha; D018036:Selenium Compounds / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; D010936:Plant Extracts; D011134:Polysaccharides; D018036:Selenium Compounds; D051176:beta Catenin
keywords: GSK-3β; antitumor activity; ovarian cancer; selenium-enriched polysaccharides; β-catenin