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

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.

• Authors: Pallavi Banerjee, Aninda Basu, Jack L Arbiser, Soumitro Pal
• Journal: Cancer letters (Cancer Lett) Vol. 338 Issue 2 Pg. 292-9 (Sep 28 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 23752066 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 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

Topics

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