2-phenylethynesulphonamide (PFT-μ) enhances the anticancer effect of the novel hsp90 inhibitor NVP-AUY922 in melanoma, by reducing GSH levels
Issue date
2016Author
Veà Jódar, Àlvar
Benítez, Sandra
Domingo, Mónica
Santacana Espasa, Maria
Valls Marsal, Joan
Vilella, Ramón
Marti, Rosa M.
Suggested citation
Yeramian Hakim, Andree;
Veà Jódar, Àlvar;
Benítez, Sandra;
Ribera i Calvet, Joan;
Domingo, Mónica;
Santacana Espasa, Maria;
...
Marti, Rosa M..
(2016)
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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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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.