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Oncotarget. 2016 May 10;7(19):28369-83. doi: 10.18632/oncotarget.8619.

Selenium-enriched polysaccharides from Pyracantha fortuneana (Se-PFPs) inhibit the growth and invasive potential of ovarian cancer cells through inhibiting β-catenin signaling.

Author information

1
College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China.
2
Renhe Hospital of China Three Gorges University, Yichang, HuBei 443002, China.
3
Molecular Medicine & Cancer Research Center, Chongqing Medical University, Chongqing 400016, China.
4
Department of Pharmacology, Hubei Institute for Nationalities, Enshi, HuBei 445000, China.

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.

KEYWORDS:

GSK-3β; antitumor activity; ovarian cancer; selenium-enriched polysaccharides; β-catenin

PMID:
27058760
PMCID:
PMC5053732
DOI:
10.18632/oncotarget.8619
[Indexed for MEDLINE]
Free PMC Article

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