Abstract

BackgroundSeveral efforts have been deployed to cure osteosarcoma, a high-grade malignant bone tumour in children and adolescents. However, some challenges such as drug resistance, relapse, and tumour metastasis remain owing to the existence of cancer stem cells (CSC). There is an urgent need to develop cost-effective and safe therapies.MethodsWogonin, an extract from the root of Scutellaria baicalensis, has long been considered as a promising natural and safe compound for anti-tumourigenesis, particularly to inhibit tumour invasion and metastasis. Hoechst 33,342 staining, wound healing assay, sphere formation assay, western blotting, and gelatin zymography assays were performed in CD133 positive osteosarcoma cell.ResultsIn this study, we examined the effect of Wogonin on the mobility of human osteosarcoma CSC. Wogonin induces apoptosis of human osteosarcoma CSC, inhibits its mobility in vitro via downregulation of MMP-9 expression, and represses its renewal ability.ConclusionsWe demonstrated that Wogonin decreases the renewal capacity of CSC. By inhibiting the formation of and reducing the size of spheres, Wogonin at a concentration of 40–80 μM effectively minimizes potential risk from CSC. Taken together, we have demonstrated a new approach for developing a potential therapy for osteosarcoma.

Highlights

  • Several efforts have been deployed to cure osteosarcoma, a high-grade malignant bone tumour in children and adolescents

  • We aimed to evaluate the inhibitory effect of Wogonin on the invasion of CD133+ Cal72 human osteosarcoma stem cell, a critical step in metastasis of the tumour exhibited by the downregulation of Matrix Metalloproteinases-9 (MMP-9), and to elucidate the effects of Wogonin on the sphere formation ability of cancer stem cells (CSC) to design a novel, natural, and safer anti-mobility and anti-invasion agent

  • We hypothesized that human osteosarcoma CSC, which were isolated by Mongre et al [14], are considered as the main determinant in osteosarcoma relapse [16] and are probably suppressed by Wogonin

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Summary

Introduction

Several efforts have been deployed to cure osteosarcoma, a high-grade malignant bone tumour in children and adolescents Some challenges such as drug resistance, relapse, and tumour metastasis remain owing to the existence of cancer stem cells (CSC). Several efforts have been deployed to cure osteosarcoma, which combine surgery and various chemotherapies or radiation [1,2,3] These strategies are not completely effective and meet with difficulties such as drug resistance, relapse, and, tumour metastasis [4, 5]. The primary cause of death in patients with osteosarcoma is pulmonary metastasis [4], as reported by Geller et al [5], the capability of cancer stem cells (CSC) to cause tumour relapse is of great concern. The prevention of metastasis in osteosarcoma CSC is imperative

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