2. Academic Validation
  3. Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor

Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor

  • Cancers (Basel). 2022 Feb 3;14(3):782. doi: 10.3390/cancers14030782.
Husvinee Sundaramurthi 1 2 3 4,  Sandra García-Mulero 5 6,  Valentina Tonelotto 1 2 7,  Kayleigh Slater 1 2,  Simone Marcone 8,  Josep M Piulats 5 9,  Ronald William Watson 1 4,  Desmond J Tobin 1 10,  Lasse D Jensen 11,  Breandán N Kennedy 1 2
Affiliations

Affiliations

  • 1 UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland.
  • 2 UCD School of Biomolecular and Biomedical Science, University College Dublin, D04 V1W8 Dublin, Ireland.
  • 3 Systems Biology Ireland, University College Dublin, D04 V1W8 Dublin, Ireland.
  • 4 UCD School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland.
  • 5 Cancer Immunotherapy (CIT) Group-iPROCURE, Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
  • 6 Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
  • 7 Xenopat S.L., Business Bioincubator, Bellvitge Health Science Campus, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
  • 8 Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin St. James's Hospital, D08 W9RT Dublin, Ireland.
  • 9 Medical Oncology Department, Catalan Institute of Cancer (ICO) and CIBERONC, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
  • 10 The Charles Institute for Dermatology, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland.
  • 11 BioReperia AB, Wahlbecksgatan, 582 16 Linköping, Sweden.
PMID: 35159049 DOI: 10.3390/cancers14030782
Abstract

Metastatic uveal melanoma (MUM) is characterized by poor patient survival. Unfortunately, current treatment options demonstrate limited benefits. In this study, we evaluate the efficacy of ACY-1215, a histone deacetylase inhibitor (HDACi), to attenuate growth of primary ocular UM cell lines and, in particular, a liver MUM cell line in vitro and in vivo, and elucidate the underlying molecular mechanisms. A significant (p = 0.0001) dose-dependent reduction in surviving clones of the primary ocular UM cells, Mel270, was observed upon treatment with increasing doses of ACY-1215. Treatment of OMM2.5 MUM cells with ACY-1215 resulted in a significant (p = 0.0001), dose-dependent reduction in cell survival and proliferation in vitro, and in vivo attenuation of primary OMM2.5 xenografts in zebrafish larvae. Furthermore, flow cytometry revealed that ACY-1215 significantly arrested the OMM2.5 cell cycle in S phase (p = 0.0001) following 24 h of treatment, and significant Apoptosis was triggered in a time- and dose-dependent manner (p < 0.0001). Additionally, ACY-1215 treatment resulted in a significant reduction in OMM2.5 p-ERK expression levels. Through proteome profiling, the attenuation of the microphthalmia-associated transcription factor (MITF) signaling pathway was linked to the observed anti-cancer effects of ACY-1215. In agreement, pharmacological inhibition of MITF signaling with ML329 significantly reduced OMM2.5 cell survival and viability in vitro (p = 0.0001) and reduced OMM2.5 cells in vivo (p = 0.0006). Our findings provide evidence that ACY-1215 and ML329 are efficacious against growth and survival of OMM2.5 MUM cells.

Keywords

ACY-1215; HDAC inhibitor; MITF; ML329; metastatic uveal melanoma; p-ERK; zebrafish xenografts.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z