RETRACTED: Lupeol Induces Apoptosis and Cell Cycle Arrest of Human Osteosarcoma Cells Through PI3K/AKT/mTOR Pathway

Abstract

Lupeol, a dietary triterpene present in many fruits and medicinal plants, has been reported to possess many pharmacological properties including anticancer effect in vitro and in vivo However, the activity of lupeol against osteosarcoma remains unclear. The present study is conducted to investigate the anticancer activity and the underlying mechanisms of lupeol on human osteosarcoma cells (MNNG/HOS and MG-63) in vitro and in vivo MNNG/HOS and MG-63 cells were treated by lupeol and subjected to methyl thiazolyl tetrazolium analysis, Hoechst staining, annexin V/propidium iodide double staining, cell cycle analysis, and Western blot analysis. In addition, MNNG/HOS xenograft tumors were established in female nude BALB/c mice, and lupeol was intravenously administered to evaluate the anticancer capacity in vivo Our results showed that lupeol induced apoptosis as well as cell cycle arrest in G0/G1 phase of MNNG/HOS and MG-63 cells in a dose-dependent manner in vitro Furthermore, the protein expression levels of phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-AKT), p-p70S6K, and cyclin D1 were significantly downregulated, whereas the expression levels of p21 and p27 were upregulated. These protein interactions may play a pivotal role in the regulation of apoptosis and cell cycle arrest. More importantly, our in vivo studies showed that administration of lupeol decreased tumor growth in a dose-dependent manner and has no significant effect on the function of liver and kidney. Taken together, our findings indicated that lupeol can induce apoptosis as well as cell cycle arrest of human osteosarcoma cells through phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway and might offer a promising new approach in the effective treatment of osteosarcoma.

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

“…For example, Yang et al [33] found that XBP1 exerted its effect on OS probably by influencing PI3K/mTOR signalling. A study performed by Liu et al [34] showed that lupeol can induce apoptosis as well as cell cycle arrest of human OS cells through phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway. However, it is unknown whether PI3K/AKT/mTOR signalling pathway mediated the anti-cancer effect of CuE.…”

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

“…It is often reported that the PI3K/Akt/mTOR signaling pathway works abnormally in cancer cells, and even being constitutively activated, which promotes the growth and proliferation of tumor cells (18). This may be due to one or more cellular events closely related to the incidence and development of cancers, such as mutation or deletion of PTEN, mutation of TSC1/2, tyrosine kinase receptor growth factor and type I PI3K, overexpression of Akt, inhibition of mTOR, exposure to carcinogens, which may lead to the activation of PI3K/Akt/mTOR, thereby inhibiting the autophagy of cells (25,26). The results demonstrated that honokiol significantly suppressed PI3K, p-Akt and p-mTOR protein expression of MG-63 cell.…”

GPNMB silencing suppresses the proliferation and metastasis of osteosarcoma cells by blocking the PI3K/Akt/mTOR signaling pathway

“…In addition, researchers have confirmed that abnormalities in the PI3K/Akt/mTOR signaling pathway are involved in the carcinogenesis of various cancers, including osteosarcoma (18,19). This pathway is reportedly activated in osteosarcoma and its suppression could inhibit the proliferation and invasion of osteosarcoma cells (19). Ono et al (20) demonstrated that the extracellular fragment of GPNMB has neuroprotective effects and activates PI3K/Akt pathway.…”

“…This pathway plays a pivotal role in a variety of biological activities that regulate cell growth, survival and migration (17). In addition, researchers have confirmed that abnormalities in the PI3K/Akt/mTOR signaling pathway are involved in the carcinogenesis of various cancers, including osteosarcoma (18,19). This pathway is reportedly activated in osteosarcoma and its suppression could inhibit the proliferation and invasion of osteosarcoma cells (19).…”