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Orellanine specifically targets renal clear cell carcinoma.

Journal article
Authors Lisa Buvall
Heidi Hedman
Alina Khramova
Deman Hadi Najar
Lovisa Bergwall
Kerstin Ebefors
Carina Sihlbom
Sven Lundstam
Anders Herrmann
Hanna Wallentin
Emelie Roos
Ulf Nilsson
Martin Johansson
Jan Törnell
Börje Haraldsson
Jenny Nyström
Published in Oncotarget
Volume 8
Issue 53
Pages 91085-91098
ISSN 1949-2553
Publication year 2017
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Physiology
Core Facilities, Proteomics
Institute of Clinical Sciences, Department of Urology
Institute of Medicine
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 91085-91098
Language en
Links dx.doi.org/10.18632/oncotarget.1955...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Cancer and Oncology, Kidney diseases

Abstract

Renal cell carcinoma (RCC), arising from the proximal tubule in the kidney, accounts for approximately 85% of kidney cancers and causes over 140,000 annual deaths worldwide. In the last decade, several new therapies have been identified for treatment of metastatic RCC. Although these therapies increase survival time compared to standard care, none of them has curative properties. The nephrotoxin orellanine specifically targets proximal tubular epithelial cells, leaving other organs unaffected. We therefore hypothesized that the selective toxicity of orellanine extends to clear cell RCC (ccRCC) cells since they emanate from proximal tubular cells. Orellanine would thus target both primary and metastatic ccRCC in vitro and in vivo. We found that orellanine induces dose-dependent cell death in proximal tubular cells and in all ccRCC cells tested, both primary and cell lines, with no toxicity detected in control cells. The toxic action of orellanine involve decreased protein synthesis, disrupted cell metabolism and induction of apoptosis. In nude rats carrying human ccRCC xenografts, brief orellanine treatment eliminated more than 90% of viable tumor mass compared to control rats.This identifies orellanine as a potential treatment concept for ccRCC patients on dialysis, due to its unique selective toxicity towards ccRCC.

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