ACY 1215, a histone deacetylase 6 inhibitor, inhibits cancer cell growth in melanoma

Abstract

Histone deacetylase 6 (HDAC6) plays critical roles in dozens of malignant cancers, including melanoma. Therefore, inhibition of HDAC6 can be a potential strategy of targeting melanoma. ACY 1215 (ricolinostat), a selective HDAC6 inhibitor, is currently being clinically trialed in multiple cancers but not in melanoma. In this study, we tested the pre-clinical efficacy of ACY 1215 in melanoma cell lines. First, we found higher HDAC6 expression in melanoma cell lines than in an epidermal melanocyte cell line. Then, we observed the dose- and time-dependent reduction of cell proliferation caused by ACY 1215 treatment. Proliferation inhibition by ACY 1215 was associated with accumulation of acetylated tubulin but did not affect histone H3K9 acetylation. In addition, ACY 1215 induced cell apoptosis and G0/G1 cell cycle arrest. Finally, we show that ACY 1215 reduced tumor burden and increased survival in an in vivo mouse cell line xenograft model. All of these pre-clinical data indicate that HDAC6 is a potential target in melanoma, and that targeting HDAC6 in melanoma using ACY 1215 may be translationally relevant.