Orellanine specifically targets renal clear cell carcinoma
| Autor: | Heidi Hedman, Lovisa Bergwall, Emelie Roos, Kerstin Ebefors, Deman Najar, Anders Herrmann, Börje Haraldsson, Sven Lundstam, Alina Khramova, Jan Törnell, Martin Johansson, Ulf Nilsson, Jenny Nyström, Hanna Wallentin, Carina Sihlbom, Lisa Buvall |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Pathology medicine.medical_specialty Necrosis clear cell renal cell carcinoma nephrotoxin necrosis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Renal cell carcinoma medicine Kidney business.industry Orellanine apoptosis medicine.disease Clear cell renal cell carcinoma 030104 developmental biology medicine.anatomical_structure Oncology chemistry Apoptosis 030220 oncology & carcinogenesis medicine.symptom business Clear cell Research Paper anti-carcinogenic treatment |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.19555 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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