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Orellanine specifically targets renal clear cell carcinoma

Buvall, Lisa; Hedman, Heidi; Khramova, Alina; Najar, Deman; Bergwall, Lovisa; Ebefors, Kerstin; Sihlbom, Carina; Lundstam, Sven; Herrmann, Anders and Wallentin, Hanna, et al. (2017) In Oncotarget 8(53). p.91085-91098
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... (More)

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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publication status
published
subject
keywords
Anti-carcinogenic treatment, Apoptosis, Clear cell renal cell carcinoma, Necrosis, Nephrotoxin
in
Oncotarget
volume
8
issue
53
pages
14 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85032686026
  • wos:000414175500051
ISSN
1949-2553
DOI
10.18632/oncotarget.19555
language
English
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yes
id
11496274-1e4f-4d54-9c1e-77bd2d6d93df
date added to LUP
2017-12-12 16:14:38
date last changed
2018-09-09 04:56:32
@article{11496274-1e4f-4d54-9c1e-77bd2d6d93df,
  abstract     = {<p>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.</p>},
  author       = {Buvall, Lisa and Hedman, Heidi and Khramova, Alina and Najar, Deman and Bergwall, Lovisa and Ebefors, Kerstin and Sihlbom, Carina and Lundstam, Sven and Herrmann, Anders and Wallentin, Hanna and Roos, Emelie and Nilsson, Ulf A. and Johansson, Martin and Törnell, Jan and Haraldsson, Börje and Nyström, Jenny},
  issn         = {1949-2553},
  keyword      = {Anti-carcinogenic treatment,Apoptosis,Clear cell renal cell carcinoma,Necrosis,Nephrotoxin},
  language     = {eng},
  number       = {53},
  pages        = {91085--91098},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Orellanine specifically targets renal clear cell carcinoma},
  url          = {http://dx.doi.org/10.18632/oncotarget.19555},
  volume       = {8},
  year         = {2017},
}