2-phenylethynesulphonamide (PFT-μ) enhances the anticancer effect of the novel hsp90 inhibitor NVP-AUY922 in melanoma, by reducing GSH levels.

Autor:	Yeramian, Andree, Vea, Alvar, Benítez, Sandra, Ribera, Joan, Domingo, Mónica, Santacana, Maria, Martinez, Montserrat, Maiques, Oscar, Valls, Joan, Dolcet, Xavier, Vilella, Ramón, Cabiscol, Elisa, Matias ‐ Guiu, Xavier, Marti, Rosa M.
Předmět:	MELANOMA treatment SULFONAMIDE drugs HEAT shock proteins ANTINEOPLASTIC agents PHYSIOLOGICAL effects of glutathione OXIDATIVE stress NF-kappa B
Zdroj:	Pigment Cell & Melanoma Research; May2016, Vol. 29 Issue 3, p352-371, 20p
Abstrakt:	Heat shock proteins (HSPs), are molecular chaperones that assist the proper folding of nascent proteins. This study aims to evaluate the antitumour effects of the hsp90 inhibitor NVP-AUY922 in melanoma, both in vitro and in vivo. Our results show that NVP-AUY922 inhibits melanoma cell growth in vitro, with down regulation of multiple signalling pathways involved in melanoma progression such as NF-ĸB and MAPK/ERK. However, NVP-AUY922 was unable to limit tumour growth in vivo. Cotreatment of A375M xenografts with NVP-AUY922 and PFT-μ, a dual inhibitor of both hsp70 and autophagy, induced a synergistic increase of cell death in vitro, and delayed tumour formation in A375M xenografts. PFT-μ depleted cells from the reduced form of glutathione (GSH) and increased oxidative stress. The oxidative stress induced by PFT-μ further enhanced NVP-AUY922-induced cytotoxic effects. These data suggest a potential therapeutic role for NVP-AUY922 used in combination with PFT-μ, in melanoma. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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