Oncotarget

Research Papers:

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

Qianling Sun, Mengmeng Dong, Zhihui Wang, Changdong Wang, Deqiao Sheng, Zhihong Li, Debin Huang and Chengfu Yuan _

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Oncotarget. 2016; 7:28369-28383. https://doi.org/10.18632/oncotarget.8619

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Abstract

Qianling Sun1,*, Mengmeng Dong1,*, Zhihui Wang2,*, Changdong Wang3, Deqiao Sheng1, Zhihong Li1, Debin Huang4, Chengfu Yuan1

1College of Medical Science, China Three Gorges University, Yichang, HuBei 443002, China

2Renhe Hospital of China Three Gorges University, Yichang, HuBei 443002, China

3Molecular Medicine & Cancer Research Center, Chongqing Medical University, Chong qing 400016, China

4Department of Pharmacology, Hubei Institute for Nationalities, Enshi, HuBei 445000, China

*These authors have contributed equally to this work

Correspondence to:

Chengfu Yuan, email: [email protected]

Keywords: selenium-enriched polysaccharides, ovarian cancer, antitumor activity, GSK-3β, β-catenin

Received: December 6, 2015    Accepted: March 18, 2016    Published: April 06, 2016

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.


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