Cucurbitacin B inhibits the stemness and metastatic abilities of NSCLC via downregulation of canonical Wnt/β-catenin signaling axis
Genre
Journal ArticleDate
2016-02-24Author
Shukla, SSinha, S
Khan, S
Kumar, S
Singh, K
Mitra, K
Maurya, R
Meeran, SM
Subject
A549 CellsAnimals
Blotting, Western
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic
Down-Regulation
Epithelial-Mesenchymal Transition
Female
Human Umbilical Vein Endothelial Cells
Humans
Immunoprecipitation
Lung Neoplasms
Mice
Microscopy, Fluorescence
Neovascularization, Physiologic
Nitrosamines
RNA Interference
RNA, Small Interfering
Transforming Growth Factor beta1
Triterpenes
Wnt Signaling Pathway
Wnt3 Protein
Wnt3A Protein
beta Catenin
Permanent link to this record
http://hdl.handle.net/20.500.12613/5146
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10.1038/srep21860Abstract
Lack of effective anti-metastatic drugs creates a major hurdle for metastatic lung cancer therapy. For successful lung cancer treatment, there is a strong need of newer therapeutics with metastasis-inhibitory potential. In the present study, we determined the anti-metastatic and anti-angiogenic potential of a natural plant triterpenoid, Cucurbitacin B (CuB) against non-small cell lung cancer (NSCLC) both in vitro and in vivo. CuB demonstrated a strong anti-migratory and anti-invasive ability against metastatic NSCLC at nanomolar concentrations. CuB also showed significant tumor angiogenesis-inhibitory effects as evidenced by the inhibition of migratory, invasive and tube-forming capacities of human umbilical vein endothelial cells. CuB-mediated inhibition of angiogenesis was validated by the inhibition of pre-existing vasculature in chick embryo chorio-allantoic membrane and matrigel plugs. Similarly, CuB inhibited the migratory behavior of TGF-β1-induced experimental EMT model. The CuB-mediated inhibition of metastasis and angiogenesis was attributable to the downregulation of Wnt/β-catenin signaling axis, validated by siRNA-knockdown of Wnt3 and Wnt3a. The CuB-mediated downregulation of Wnt/β-catenin signaling was also validated using 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis model in vivo. Collectively, our findings suggest that CuB inhibited the metastatic abilities of NSCLC through the inhibition of Wnt/β-catenin signaling axis.Citation to related work
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http://dx.doi.org/10.34944/dspace/5128