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

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.

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…Cucurbitacins have multiple therapeutic effects such as anti-inflammation, anti-proliferation, antiangiogenesis, and anti-cancer [452,[459][460][461][462]. Besides, cucurbitacins have also been elucidated as a potential candidate for various cancer therapies, including oral cell carcinoma, breast, ovarian, prostate, lung, gastric, bladder, and thyroid cancers, neuroastoma, hepatoma, and osteosarcoma [463][464][465][466][467][468][469][470][471][472][473][474][475]. Most of cucurbitacins have been reported with various anti-cancer activities, such as pro-apoptosis, anti-angiogenesis, autophagy induction, and inhibition of metastasis [452,[460][461][462]476].…”

Cucurbitacin E Inhibits Huh7 Hepatoma Carcinoma Cell Proliferation and Metastasis via Suppressing MAPKs and JAK/STAT3 Pathways

“…Cucurbitacins are a family of natural products isolated from Cucurbitaceae plants, and possess a wide spectrum of pharmacological effects including anti-cancer, anti-diabetic, cytoprotective, and anti-inflammatory activities [15][16][17][18]. Cucurbitacin E (CuE), a highly oxygenated triterpene of cucurbitacins, is known to have a variety of pharmacological effects such as hepatoprotective, anti-inflammatory and anti-cancer activities [19][20][21][22][23][24]. Previous investigations have shown that CuE inhibits cell proliferation, migration, and invasion through different molecular mechanisms in vitro and in vivo, indicating that CuE exerts prominent investigation prospect in the treatment of various cancers.…”

Honokiol induces autophagy and apoptosis of osteosarcoma through PI3K/Akt/mTOR signaling pathway

“…Many diseases, including cancer, autoimmune diseases and neuropathy, are caused by disorders of the PI3K-Akt-mTOR signaling pathway (10). The PI3K-Akt-mTOR signaling pathway is related to several important mechanisms of cell growth, so a better understanding of the PI3K-Akt-mTOR signaling pathway contributes to the development of cancer drugs, and mTOR inhibitors have been previously developed and applied as novel antitumor targeting drugs (11).…”