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Title: Glaucarubinone inhibits colorectal cancer growth by suppression of hypoxia-inducible factor 1α and β-catenin via a p-21 activated kinase 1-dependent pathway.
Austin Authors: Huynh, Nhi;Beutler, John A;Shulkes, Arthur;Baldwin, Graham S;He, Hong 
Affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 22-Oct-2014
Publication information: Biochimica Et Biophysica Acta 2014; 1853(1): 157-65
Abstract: p-21-Activated kinase 1 (PAK1) enhances colorectal cancer (CRC) progression by stimulating Wnt/β-catenin, ERK and AKT pathways. PAK1 also promotes CRC survival via up-regulation of hypoxia-inducible factor 1α (HIF-1α), a key player in cancer survival. Glaucarubinone, a quassinoid natural product, inhibits pancreatic cancer growth by down-regulation of PAK1. The aim of this study was to investigate the effect of glaucarubinone on CRC growth and metastasis, and the mechanism involved. Cell proliferation was measured in vitro by [(3)H]-thymidine incorporation and in vivo by volume of tumor xenografts. Protein concentrations were measured by Western blotting of cell extracts. We report here that glaucarubinone inhibited CRC growth both in vitro and in vivo. The potency of glaucarubinone as an inhibitor of cell proliferation was negatively correlated to PAK1 expression in CRC cells. Glaucarubinone suppressed the expression of HIF-1α and β-catenin. Knockdown of PAK1 by shRNA enhanced inhibition by glaucarubinone while constitutively active PAK1 blocked the inhibitory effect. Our findings indicate that glaucarubinone inhibited CRC growth by down-regulation of HIF-1α and β-catenin via a PAK1-dependent pathway.
Gov't Doc #: 25409929
DOI: 10.1016/j.bbamcr.2014.10.013
Type: Journal Article
Subjects: CRC
Cell Line, Tumor
Cell Proliferation.drug effects
Colorectal Neoplasms.drug therapy.pathology
Glaucarubin.analogs & derivatives.pharmacology
Hypoxia-Inducible Factor 1, alpha Subunit.antagonists & inhibitors
beta Catenin.antagonists & inhibitors
p21-Activated Kinases.physiology
Appears in Collections:Journal articles

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