title: 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.affiliation: Division of Nephrology, Children's Hospital, Boston, MA 02115, USA.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Banerjee
authors.forename: Aninda
authors.initials: A
authors.lastname: Basu
authors.forename: Jack L
authors.initials: JL
authors.lastname: Arbiser
authors.forename: Soumitro
authors.initials: S
authors.lastname: Pal
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D065095:Calcineurin Inhibitors; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016572:Cyclosporine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017705:Lignans / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D048490:raf Kinases / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D019703:Calcineurin; D065095:Calcineurin Inhibitors; D016572:Cyclosporine; D051547:Heme Oxygenase-1; D017705:Lignans; D000090063:Proto-Oncogene Mas; D042461:Vascular Endothelial Growth Factor A; D048490:raf Kinases; D018631:ras Proteins; C000715470:MAS1 protein, human; C467484:VEGFA protein, human; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C496541:HMOX1 protein, human
keywords: HO-1; Honokiol; Ras; Renal tumor; VEGF