Gamabufogenin and Lung-Neoplasms

Gamabufogenin has been researched along with Lung-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for Gamabufogenin and Lung-Neoplasms

ArticleYear
Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis by suppressing VEGFR-2 signaling pathway.
    Oncotarget, 2016, Jan-19, Volume: 7, Issue:3

    Gamabufotalin (CS-6), a main active compound isolated from Chinese medicine Chansu, has been shown to strongly inhibit cancer cell growth and inflammatory response. However, its effects on angiogenesis have not been known yet. Here, we sought to determine the biological effects of CS-6 on signaling mechanisms during angiogenesis. Our present results fully demonstrate that CS-6 could significantly inhibit VEGF triggered HUVECs proliferation, migration, invasion and tubulogenesis in vitro and blocked vascularization in Matrigel plugs impregnated in C57/BL6 mice as well as reduced vessel density in human lung tumor xenograft implanted in nude mice. Computer simulations revealed that CS-6 interacted with the ATP-binding sites of VEGFR-2 using molecular docking. Furthermore, western blot analysis indicated that CS-6 inhibited VEGF-induced phosphorylation of VEGFR-2 kinase and suppressed the activity of VEGFR-2-mediated signaling cascades. Therefore, our studies demonstrated that CS-6 inhibited angiogenesis by inhibiting the activation of VEGFR-2 signaling pathways and CS-6 could be a potential candidate in angiogenesis-related disease therapy.

    Topics: Angiogenesis Inhibitors; Animals; Aorta; Apoptosis; Blotting, Western; Bufanolides; Cell Movement; Cell Proliferation; Cells, Cultured; Endothelium, Vascular; Fluorescent Antibody Technique; Human Umbilical Vein Endothelial Cells; Humans; Immunoprecipitation; Lung Neoplasms; Mice; Mice, Inbred C57BL; Mice, Nude; Models, Molecular; Neovascularization, Physiologic; RNA, Small Interfering; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Wound Healing

2016
Quantitative proteomics reveals molecular mechanism of gamabufotalin and its potential inhibition on Hsp90 in lung cancer.
    Oncotarget, 2016, Nov-22, Volume: 7, Issue:47

    Gamabufotalin (CS-6) is a major bufadienolide of Chansu, which shows desirable metabolic stability and less adverse effect in cancer therapy. CS-6 treatment inhibited the proliferation of NSCLC in a nanomolar range. And CS-6 could induce G2/M cell cycle arrest and apoptosis in A549 cells. However, its molecular mechanism in antitumor activity remains poorly understood. We employed a quantitative proteomics approach to identify the potential cellular targets of CS-6, and found 38 possible target-related proteins. Among them, 31 proteins were closely related in the protein-protein interaction network. One of the regulatory nodes in key pathways was occupied by Hsp90. Molecular docking revealed that CS-6 interacted with the ATP-binding sites of Hsp90. In addition, CS-6 inhibited the chaperone function of Hsp90 and reduced expression of Hsp90-dependent client proteins. Moreover, CS-6 markedly down-regulated the protein level of Hsp90 in tumor tissues of the xenograft mice. Taken together, our results suggest that CS-6 might be a novel inhibitor of Hsp90, and the possible network associated with CS-6 target-related proteins was constructed, which provided experimental evidence for the preclinical value of using CS-6 as an effective antitumor agent in treatment of NSCLC.

    Topics: Animals; Antineoplastic Agents; Bufanolides; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chromatography, Liquid; HSP90 Heat-Shock Proteins; Humans; Lung Neoplasms; Mice; Models, Molecular; Molecular Conformation; Proteomics; Quantitative Structure-Activity Relationship; Tandem Mass Spectrometry

2016