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- Title
2-phenylethynesulphonamide (PFT-μ) enhances the anticancer effect of the novel hsp90 inhibitor NVP-AUY922 in melanoma, by reducing GSH levels.
- Authors
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.
- 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-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.
- Subjects
MELANOMA treatment; SULFONAMIDE drugs; HEAT shock proteins; ANTINEOPLASTIC agents; PHYSIOLOGICAL effects of glutathione; OXIDATIVE stress; NF-kappa B
- Publication
Pigment Cell & Melanoma Research, 2016, Vol 29, Issue 3, p352
- ISSN
1755-1471
- Publication type
Article
- DOI
10.1111/pcmr.12472