The natural product honokiol inhibits calcineurin inhibitor-induced and Ras-mediated tumor promoting pathways

Cancer Lett. 2013 Sep 28;338(2):292-9. doi: 10.1016/j.canlet.2013.05.036. Epub 2013 Jun 7.

Abstract

Although calcineurin inhibitors (CNIs) are very useful in preventing allograft rejection, they can mediate a rapid progression of post-transplantation malignancies. The CNI cyclosporine A (CsA) can promote renal tumor growth through activation of the proto-oncogene ras and over-expression of the angiogenic cytokine VEGF; the ras activation also induces over-expression of the cytoprotective enzyme HO-1, which promotes survival of renal cancer cells. Here, we show that the natural product honokiol significantly inhibited CsA-induced and Ras-mediated survival of renal cancer cells through the down-regulations of VEGF and HO-1. Thus, honokiol treatment may help to prevent tumor-promoting effects of CsA in transplant patients.

Keywords: HO-1; Honokiol; Ras; Renal tumor; VEGF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Biphenyl Compounds / pharmacology*
  • Calcineurin / genetics
  • Calcineurin / metabolism
  • Calcineurin Inhibitors*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclosporine / antagonists & inhibitors
  • Cyclosporine / pharmacology
  • Down-Regulation / drug effects
  • Gene Expression Regulation / drug effects
  • Genes, ras
  • Heme Oxygenase-1 / biosynthesis
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Lignans / pharmacology*
  • Phosphorylation / drug effects
  • Proto-Oncogene Mas
  • Signal Transduction / drug effects
  • Transcriptional Activation / drug effects
  • Transfection
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • raf Kinases / genetics
  • raf Kinases / metabolism
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • Biphenyl Compounds
  • Calcineurin Inhibitors
  • Lignans
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • honokiol
  • Cyclosporine
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • raf Kinases
  • Calcineurin
  • ras Proteins