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

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2016
Author
Yeramian Hakim, Andree
Veà Jódar, Àlvar
Benítez, Sandra
Ribera i Calvet, Joan
Domingo, Mónica
Santacana Espasa, Maria
Martínez Alonso, Montserrat
Maiques Carlos, Oscar
Valls Marsal, Joan
Dolcet Roca, Xavier
Vilella, Ramón
Cabiscol Català, Elisa
Matias-Guiu, Xavier
Marti, Rosa M.
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Yeramian Hakim, Andree; Veà Jódar, Àlvar; Benítez, Sandra; Ribera i Calvet, Joan; Domingo, Mónica; Santacana Espasa, Maria; ... Marti, Rosa M.. (2016) . 2-phenylethynesulphonamide (PFT-μ) enhances the anticancer effect of the novel hsp90 inhibitor NVP-AUY922 in melanoma, by reducing GSH levels. Pigment Cell and Melanoma Research, 2016, vol. 29, núm. 3, p. 352–371. https://doi.org/10.1111/pcmr.12472.
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Abstract
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-KB and MAPK/ERK. However, NVP-AUY922 was unable to limit tumour growth in vivo. Cotreatment of A375M xenografts with NVP-AUY922 and PFT-l, 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-l depleted cells from the reduced form of glutathione (GSH) and increased oxidative stress. The oxidative stress induced by PFT-l further enhanced NVP-AUY922-induced cytotoxic effects. These data suggest a potential therapeutic role for NVP-AUY922 used in combination with PFT-l, in melanoma.
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http://hdl.handle.net/10459.1/59060
DOI
https://doi.org/10.1111/pcmr.12472
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Pigment Cell and Melanoma Research, 2016, vol. 29, núm. 3, p. 352–371
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