Cucurbitacin E inhibits osteosarcoma cells proliferation and invasion through attenuation of PI3K/AKT/mTOR signalling pathway.

Ying Wang,Shumei Xu,Junfeng Zhang,Yaochi Wu

doi:10.1042/bsr20160165

Ying Wang, Shumei Xu + Show 2 more

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https://doi.org/10.1042/bsr20160165

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Abstract

Cucurbitacin E (CuE), a potent member of triterpenoid family isolated from plants, has been confirmed as an antitumour agent by inhibiting proliferation, migration and metastasis in diverse cancer. However, the effects and mechanisms of CuE on osteosarcoma (OS) have not been well understood. The present study aimed to test whether CuE could inhibit growth and invasion of OS cells and reveal its underlying molecular mechanism. After various concentrations of CuE treatment, the anti-proliferative effect of CuE was assessed using the cell counting Kit-8 assay. Flow cytometry analysis was employed to measure apoptosis of OS cells. Cell cycle distribution was analysed by propidium iodide staining. Transwell assay was performed to evaluate the effect of CuE on invasion potential of OS cells. The protein levels were measured by western blot. In addition, the potency of CuE on OS cells growth inhibition was assessed in vivo. Our results showed that CuE inhibited cell growth and invasion, induced a cell cycle arrest and triggered apoptosis and modulated the expression of cell growth, cell cycle and cell apoptosis regulators. Moreover, CuE inhibited the PI3K/Akt/mTOR pathway and epithelial–mesenchymal transition (EMT), which suppressed the invasion and metastasis of OS. In addition, we also found that CuE inhibited OS cell growth in vivo. Taken together, our study demonstrated that CuE could inhibit OS tumour growth and invasion through inhibiting the PI3K/Akt/mTOR signalling pathway. Our findings suggest that CuE can be considered to be a promising anti-cancer agent for OS.

Highlights

Osteosarcoma (OS) is the most prevalent primary malignant bone tumour and the leading cause for cancer-related death among children and adolescents [1]
We found that Cucurbitacin E (CuE) significantly inhibited the invasion of MG63 and U2OS cells compared with untreated group (Figures 4 A–4D)
CuE inhibits tumorigenesis in OS cells in vivo To further investigate the inhibitory function of CuE on OS metastasis in vivo, MG63 and U2OS cells were subcutaneously injected at the right thigh of nude mice, and treated it with different concentrations CuE (1.0 and 5.0 mg/kg)

Summary

Introduction

Osteosarcoma (OS) is the most prevalent primary malignant bone tumour and the leading cause for cancer-related death among children and adolescents [1]. The development of novel therapies for the management of OS is especially urgent. Increasing evidence supports that natural agents open up a novel avenue for treatment of cancers, especially by combining with conventional therapeutics [7]. Cucurbitacin E (CuE), a natural tetracyclic triterpenoid, is an abundant member of the cucurbitacin family, which is widely distributed in the plants [8]. It has been well documented that cucurbitacins inhibit growth and proliferation in various cancer cells via cell cycle arrest, and induction of apoptosis [9]. Recent observations showed that CuE suppressed the proliferation and induced apoptosis in ovarian [10,11], leukaemia [12] and pancreatic cancer cell lines [13]. Limited studies have paid attention on the therapeutic effects and underlying mechanisms of CuE on OS

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