Glaucarubinone inhibits colorectal cancer growth by suppression of hypoxia-inducible factor 1α and β-catenin via a p-21 activated kinase 1-dependent pathway

N Huynh; JA Beutler; A Shulkes; GS Baldwin; H He

Journal article

Glaucarubinone inhibits colorectal cancer growth by suppression of hypoxia-inducible factor 1α and β-catenin via a p-21 activated kinase 1-dependent pathway

N Huynh, JA Beutler, A Shulkes, GS Baldwin, H He

Biochimica Et Biophysica Acta Molecular Cell Research | ELSEVIER SCIENCE BV | Published : 2015

DOI: 10.1016/j.bbamcr.2014.10.013

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 [3H]-thymidine incorporation and in vivo by volume of tumor xenografts. Protein concentrations were measured by Western blotting of cell extracts. We report here that g..

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University of Melbourne Researchers

Arthur Shulkes Author

Hong He Author

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Grants

Awarded by National Cancer Institute

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council (NHMRC) of Australia grants 508908 (HH) and 1041831 (GB & AS), by the Austin Hospital Medical Research Foundation 2-1281 (HH), and by the Intramural Research Program of the NIH National Cancer Institute Center for Cancer Research 1 ZIA BC011470 02 (JB).