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.
Highlights
Ovarian cancer (OC) is the most lethal gynecological malignancy with obstinate abilities of invasion and metastasis [1]
Primary antibodies to Bax, Bcl-2, E-cadherin, N-cadherin, Cytokeratin 19, Vimentin, ZEB1, ZEB2, matrix metalloproteinase (MMP)-9, β-catenin, GSK-3β, CyclinD1, phosphorylated GSK-3β, phosphorylated β-catenin, cleaved caspase-3 and poly polymerase (PARP) were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). α-tubulin and lamin A/C antibodies, MG132 was purchased from Sigma
To clarify whether reduced cell proliferation after successfully purified Se-enriched polysaccharides from Pyracantha fortuneana (Se-PFPs) treatment is caused by cell death, we carried out cell apoptosis assays using multiple methods
Summary
Ovarian cancer (OC) is the most lethal gynecological malignancy with obstinate abilities of invasion and metastasis [1]. Because the early symptoms of OC are too atypical to diagnose, the primary tumor in the majority of OC patients has already been metastasized to other tissues or organs when it was diagnosed [2]. The majority of OC patients who initially present with advanced disease will relapse [5]. Increasing evidence demonstrated that chemoresistance is highly associated with acquiring the www.impactjournals.com/oncotarget capacity of epithelial to mesenchymal transition (EMT) in ovarian cancer cells [6]. Major signaling pathways such as Wnt/β-catenin, TGF-β and Notch are involved in EMT in OC cells [7, 8]
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