Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Compelling evidence indicates that bone marrow-derived endothelial progenitor cells (EPCs) can contribute to postnatal neovascularization and tumor angiogenesis. EPCs have been shown to play a "catalytic" role in metastatic progression by mediating the angiogenic switch. Understanding the pharmacological functions and molecular targets of natural products is critical for drug development. Butein, a natural chalcone derivative, has been reported to exert potent anticancer activity. However, the antiangiogenic activity of butein has not been addressed. In this study, we found that butein inhibited serum- and vascular endothelial growth factor- (VEGF-) induced cell proliferation, migration, and tube formation of human EPCs in a concentration dependent manner without cytotoxic effect. Furthermore, butein markedly abrogated VEGF-induced vessels sprouting from aortic rings and suppressed microvessel formation in the Matrigel implant assay in vivo. In addition, butein concentration-dependently repressed the phosphorylation of Akt, mTOR, and the major downstream effectors, p70S6K, 4E-BP1, and eIF4E in EPCs. Taken together, our results demonstrate for the first time that butein exhibits the antiangiogenic effect both in vitro and in vivo by targeting the translational machinery. Butein is a promising angiogenesis inhibitor with the potential for treatment of cancer and other angiogenesis-related diseases.
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PMID:Butein Inhibits Angiogenesis of Human Endothelial Progenitor Cells via the Translation Dependent Signaling Pathway. 2384 Feb 71

Cervical cancer is the second most common women carcinoma worldwide and the fourth leading cause of cancer-associated mortality in women. Butein, a bioactive flavonoid isolated from numerous native plants, has been shown to induce apoptosis and inhibits migration and invasion in numerous human cancer cells. However, to the best of our knowledge, the effect of butein on human cervical cancer cells has not been reported. The present study aimed to determine the effect of butein on cell growth, apoptosis, migration and invasion and identify the associated molecular mechanism involved using HeLa human cervical cancer cells in vitro, and on tumor growth in a nude mouse model. It was found that butein notably inhibited cell viability, colony formation, migration and invasion, induced cell cycle at the G2/M stage and cell apoptosis, as well as enhanced caspase-3, -8 and -9 activity in HeLa cells in a dose-dependent manner. When administered intraperitoneally, butein inhibited the tumor growth of human cervical cancer xenograft tumors in the nude mouse model. Additionally, treatment with butein significantly increased reactive oxygen species (ROS) generation and reduced the phosphorylation of PI3K, AKT and mTOR expression, which contributes to the inhibition of the tumor growth of cervical cancer and reduction of oxidative stress. These findings suggested that butein serves as a potential therapeutic agent for the treatment of cervical cancer.
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PMID:Butein suppresses cervical cancer growth through the PI3K/AKT/mTOR pathway. 2596 38