Anticancer Activity of Sweroside Nanoparticles in Prostate Cancer Bone Metastasis in PC-3 Cells Involved in Wnt/β-Catenin Signaling Pathway

Author:

Huang Sheng1,Zou Changye2,Xie Shangyan3,Wang Bin3,LingHu Xitao4,Wang Yixiao4,Xu Xiaohong5,Huang Shuai3,Wa Qingde4

Affiliation:

1. Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, PR China

2. Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, PR China

3. Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong, PR China

4. Department of Orthopedics, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, Guizhou, PR China

5. Department of Stomatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong, PR China

Abstract

Bone metastasis is a significant cause of morbidity and mortality in patients with prostate cancer (PCa). This study is aimed at illustrating the mechanism of sweroside-mediated regulation in bone metastasis in PCa cells. Owing to the limitations of antitumor drugs in terms of their physical and chemical properties, making them into nanomaterials can effectively improve drug stability and bioavailability. Apoptosis was assessed with flow cytometry using the annexin V/propidium iodide binding assay; proteins, including p53, P21, Bcl-2, and Bax; and induction of intracellular reactive oxygen species (ROS). Using colony formation assay, sphere formation assay, and the expression changes in CD133 and CD44, stem cell characteristics were assessed. Epithelial–mesenchymal transition (EMT) activity was accessed by levels of the expression changes of EMT-related markers, vimentin and E-cadherin. Wnt/β-catenin signaling pathway was examined to detect the levels of the expression changes of snail and β-catenin. PC-3 cells were treated with lithium chloride (LiCl), which is an agonist of Wnt/β-catenin signaling, and the levels of CD133, CD44, vimentin, E-cadherin, snail, and β-catenin were detected. T-cell factor/lymphocyte enhancer factor (TCF/LEF) activity in cells overexpressing β-catenin was used to detect the effects on β-catenin transcription, and the expression of c-myc, Cyclin D1, Survivin, and MMP-7 were used to detect Wnt downstream target genes. Our results suggest that sweroside induces apoptosis and intracellular ROS; upregulates apoptotic proteins; and suppresses proliferation, invasion, and migration, preventing stem cell characteristics, including sphere formation, colony formation, and CD133 and CD44 expressions. Furthermore, sweroside nanoparticles exerts inhibitory effects on β-catenin transcription by suppressing TTCF/LEF activity in cells overexpressing β-catenin and downregulation of the expression of Wnt downstream target genes, including c-myc, Cyclin D1, Survivin, and MMP-7. The potential therapeutic effect of sweroside nanoparticles on bone metastatis of PCa was suggested, by these findings.

Publisher

American Scientific Publishers

Subject

Pharmaceutical Science,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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