Your browser doesn't support javascript.
loading
Selective inhibition of HDAC6 by N-acylhydrazone derivative reduces the proliferation and induces senescence in carcinoma hepatocellular cells.
Ferreira-Silva, Guilherme Álvaro; Rodrigues, Daniel Alencar; Pressete, Carolina Girotto; Caixeta, Ester Siqueira; Gamero, Angel Mauricio Castro; Miyazawa, Marta; Hanemann, João Adolfo Costa; Fraga, Carlos Alberto Manssour; Aissa, Alexandre Ferro; Ionta, Marisa.
Afiliación
  • Ferreira-Silva GÁ; Institute of Biomedical Sciences, Federal University of Alfenas, MG 37130-001, Brazil.
  • Rodrigues DA; Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, CCS, Rio de Janeiro, RJ, Brazil.
  • Pressete CG; Institute of Biomedical Sciences, Federal University of Alfenas, MG 37130-001, Brazil.
  • Caixeta ES; Institute of Biomedical Sciences, Federal University of Alfenas, MG 37130-001, Brazil.
  • Gamero AMC; Human Genetics Laboratory, Institute of Natural Science, Federal University of Alfenas, zip-code 37130-001, Alfenas, MG, Brazil.
  • Miyazawa M; School of Dentistry, Federal University of Alfenas, 37130-001 MG, Brazil.
  • Hanemann JAC; School of Dentistry, Federal University of Alfenas, 37130-001 MG, Brazil.
  • Fraga CAM; Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, CCS, Rio de Janeiro, RJ, Brazil.
  • Aissa AF; Institute of Biomedical Sciences, Federal University of Alfenas, MG 37130-001, Brazil. Electronic address: aissa@unifesp.br.
  • Ionta M; Institute of Biomedical Sciences, Federal University of Alfenas, MG 37130-001, Brazil. Electronic address: marisa.ionta@unifal-mg.edu.br.
Toxicol In Vitro ; 99: 105884, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38945376
ABSTRACT
Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths globally. Systemic therapy is the only treatment option for HCC at an advanced stage, with limited therapeutic response. In this study, we evaluated the antitumor potential of four N-acylhydrazone (NAH) derivatives, namely LASSBio-1909, 1911, 1935, and 1936, on HCC cell lines. We have previously demonstrated that the aforementioned NAH derivatives selectively inhibit histone deacetylase 6 (HDAC6) in lung cancer cells, but their effects on HCC cells have not been explored. Thus, the present study aimed to evaluate the effects of NAH derivatives on the proliferative behavior of HCC cells. LASSBio-1911 was the most cytotoxic compound against HCC cells, however its effects were minimal on normal cells. Our results showed that LASSBio-1911 inhibited HDAC6 in HCC cells leading to cell cycle arrest and decreased cell proliferation. There was also an increase in the frequency of cells in mitosis onset, which was associated with disturbing mitotic spindle formation. These events were accompanied by elevated levels of CDKN1A mRNA, accumulation of CCNB1 protein, and sustained ERK1 phosphorylation. Furthermore, LASSBio-1911 induced DNA damage, resulting in senescence and/or apoptosis. Our findings indicate that selective inhibition of HDAC6 may provide an effective therapeutic strategy for the treatment of advanced HCC, including tumor subtypes with integrated viral genome. Further, in vivo studies are required to validate the antitumor effect of LASSBio-1911 on liver cancer.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Senescencia Celular / Carcinoma Hepatocelular / Proliferación Celular / Inhibidores de Histona Desacetilasas / Histona Desacetilasa 6 / Hidrazonas / Neoplasias Hepáticas / Antineoplásicos Límite: Humans Idioma: En Revista: Toxicol In Vitro Asunto de la revista: TOXICOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Senescencia Celular / Carcinoma Hepatocelular / Proliferación Celular / Inhibidores de Histona Desacetilasas / Histona Desacetilasa 6 / Hidrazonas / Neoplasias Hepáticas / Antineoplásicos Límite: Humans Idioma: En Revista: Toxicol In Vitro Asunto de la revista: TOXICOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido