Resibufogenin suppresses transforming growth factor-β-activated kinase 1-mediated nuclear factor-κB activity through protein kinase C-dependent inhibition of glycogen synthase kinase 3

Cancer Science
Lu LiuHongbin Deng

Abstract

Resibufogenin (RB), one of the major active compounds of the traditional Chinese medicine Chansu, has received considerable attention for its potency in cancer therapy. However, the anticancer effects and the underlying mechanisms of RB on pancreatic cancer remain elusive. Here, we found that RB inhibited the viability and induces caspase-dependent apoptosis in human pancreatic cancer cells Panc-1 and Aspc. Resibufogenin-induced apoptosis was through inhibition of constitutive nuclear factor-κB (NF-κB) activity and its target genes' expression, which was caused by downregulation of transforming growth factor-β-activated kinase 1 (TAK1) levels and suppression of IκB kinase activity in Panc-1 and Aspc cells. This induction of TAK1-mediated NF-κB inactivation by RB was associated with increased glycogen synthase kinase-3 (GSK-3) phosphorylation and subsequent suppression of its activity. Moreover, RB-induced GSK-3 phosphorylation/inactivation acted through activation of protein kinase C but not Akt. Finally, RB suppressed human pancreatic tumor xenograft growth in athymic nude mice. Thus, our findings reveal a novel mechanism by which RB suppresses TAK1-mediated NF-κB activity through protein kinase C-dependent inhibition of GSK-3...Continue Reading

References

Jul 19, 2001·Nature·C WangZ J Chen
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Mar 5, 2003·Journal of Cell Science·Bradley W Doble, James R Woodgett
Feb 8, 2006·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Dino Vilimek, Vincent Duronio
May 17, 2006·Genes & Development·Aram F HezelRonald A Depinho
Sep 5, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrei V OugolkovDaniel D Billadeau
Sep 21, 2006·Neoplasia : an International Journal for Oncology Research·Qingding WangB Mark Evers
Oct 21, 2006·Molecular Cell·Hui H ZhangBrendan D Manning
Jan 1, 2009·Nature Reviews. Drug Discovery·Véronique Baud, Michael Karin
Jan 13, 2009·Nature Cell Biology·Qinghang LiuJeffery D Molkentin
Jun 9, 2009·Cancer Biology & Therapy·Catherine E WharryMichael J May
Mar 2, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Huan DengJ Kelley Bentley
Apr 30, 2010·The New England Journal of Medicine·Manuel Hidalgo
Dec 28, 2010·International Immunopharmacology·Fanghua QiWei Tang
Jul 12, 2011·Journal of the National Cancer Institute·Davide MelisiPaul J Chiao
Jan 31, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Richard R KewKenneth B Marcu
Feb 4, 2012·Genes & Development·Matthew S Hayden, Sankar Ghosh
Feb 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Emily OmoriJun Ninomiya-Tsuji
Mar 23, 2012·Immunological Reviews·Shao-Cong Sun
Mar 27, 2012·Expert Opinion on Therapeutic Targets·Carmine Carbone, Davide Melisi
Oct 31, 2013·Advances in Biological Regulation·James A McCubreyLinda S Steelman
Dec 17, 2014·BMC Complementary and Alternative Medicine·Jian-Hua YinLu-Ming Liu
Apr 19, 2015·Journal of Experimental & Clinical Cancer Research : CR·Tao YangZhangqun Ye
Jul 7, 2015·HPB : the Official Journal of the International Hepato Pancreato Biliary Association·Selvi KunnimalaiyaanMuthusamy Kunnimalaiyaan
Aug 25, 2015·Pharmacology & Therapeutics·Cindy NeuzilletPascal Hammel
Mar 30, 2017·Journal of Asian Natural Products Research·Fang HuaZhuo-Wei Hu
Jul 18, 2017·Advances in Biological Regulation·Miguel A HermidaNick R Leslie
Sep 12, 2017·Annals of the New York Academy of Sciences·Do-Hee KimHye-Kyung Na

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Citations

Jul 12, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Qian LiPing Mo
Mar 18, 2020·Expert Opinion on Therapeutic Targets·Li Ding, Daniel D Billadeau
May 13, 2020·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Hui YinDi-Hao Wen
Mar 3, 2020·Experimental Gerontology·Dae Hyun KimHae Young Chung

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Methods Mentioned

BETA
nuclear translocation
xenografts
Feature Extraction
transfection
PCR
fluorescence microscopy
flow cytometry
xenograft

Software Mentioned

Python
Feature Extraction
GraphPad Prism
Prism
GeneSpring

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