Head and neck cancer cells and xenografts are very sensitive to palytoxin: decrease of c-jun n-terminale kinase-3 expression enhances palytoxin toxicityReportar como inadecuado




Head and neck cancer cells and xenografts are very sensitive to palytoxin: decrease of c-jun n-terminale kinase-3 expression enhances palytoxin toxicity - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Molecular Cancer

, 12:12

First Online: 14 February 2013Received: 09 August 2012Accepted: 06 February 2013DOI: 10.1186-1476-4598-12-12

Cite this article as: Görögh, T., Bèress, L., Quabius, E.S. et al. Mol Cancer 2013 12: 12. doi:10.1186-1476-4598-12-12

Abstract

ObjectivesPalytoxin PTX, a marine toxin isolated from the Cnidaria zooanthid Palythoa caribaeorum is one of the most potent non-protein substances known. It is a very complex molecule that presents both lipophilic and hydrophilic areas. The effect of PTX was investigated in a series of experiments conducted in head and neck squamous cell carcinoma HNSCC cell lines and xenografts.

Materials and methodsCell viability, and gene expression of the sodium-potassium-transporting ATPase subumit alpha1 ATP1AL1 and GAPDH were analyzed in HNSCC cells and normal epithelial cells after treatment with PTX using cytotoxicity-, clonogenic-, and enzyme inhibitor assays as well as RT-PCR and Northern Blotting. For xenograft experiments severe combined immunodeficient SCID mice were used to analyze tumor regression. The data were statistically analyzed using One-Way Annova SPSS vs20.

ResultsSignificant toxic effects were observed in tumor cells treated with PTX LD50 of 1.5 to 3.5 ng-ml in contrast to normal cells. In tumor cells PTX affected both the release of LDH and the expression of the sodium-potassium-transporting ATPase subunit alpha1 gene suggesting loss of cellular integrity, primarily of the plasma membrane. Furthermore, strong repression of the c-Jun N-terminal kinase 3 JNK3 mRNA expression was found in carcinoma cells which correlated with enhanced toxicity of PTX suggesting an essential role of the mitogen activated protein kinase MAPK-JNK signalling cascades pathway in the mechanisms of HNSCC cell resistance to PTX. In mice inoculated with carcinoma cells, injections of PTX into the xenografted tumors resulted within 24 days in extensive tumor destruction in 75% of the treated animals LD50 of 68 ng-kg to 83 ng-kg while no tumor regression occurred in control animals.

ConclusionsThese results clearly provide evidence that PTX possesses preferential toxicity for head and neck carcinoma cells and therefore it is worth further studying its impact which may extend our knowledge of the biology of head and neck cancer.

KeywordsPalytoxin Anti-tumoral effect Head and neck carcinoma Xenografts JNK3 Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-12-12 contains supplementary material, which is available to authorized users.

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Autor: Tibor Görögh - László Bèress - Elgar S Quabius - Petra Ambrosch - Markus Hoffmann

Fuente: https://link.springer.com/



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