Melanoma cell lines are susceptible to histone deacetylase inhibitor TSA provoked cell cycle arrest and apoptosis

Karita Peltonen, Taija M. Kiviharju, Päivi M. Järvinen, Runar Ra, Marikki Laiho

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Melanoma is the most aggressive of skin cancers because of its high resistance to currently available therapy. Although melanoma cells often retain wild-type p53 tumour suppressor protein and express it at high levels, the p53 mediated apoptosis pathway is suppressed. Histone deacetylase (HDAC) inhibitors are a promising group of compounds inducing differentiation, growth arrest and apoptosis in tumour cells in preclinical studies. We have studied the cellular effects of trichostatin A (TSA), a HDAC inhibitor, in a panel of melanoma cell lines and its mechanism of action in relation to p53. TSA stabilized wild-type p53, but p53 protein accumulation was overridden by simultaneous downregulation of p53 mRNA leading to a decrease in p53 protein. While growth arrest was induced in all cell lines studied and apoptosis in most (6/7), these cellular effects were independent of the p53 status of the cells. Inhibiting p53 function by a dominant negative p53 (p53175His) confirmed that the HDAC inhibitor induced apoptosis was independent of wild-type p53, even though TSA slightly activated p53 in a reporter assay. The results indicate that while the action of TSA is independent of p53, the activation of the apoptosis pathway by the HDAC inhibitors may provide therapeutic approaches for melanoma treatment.

Original languageEnglish (US)
Pages (from-to)196-202
Number of pages7
JournalPigment Cell Research
Issue number3
StatePublished - Jun 2005
Externally publishedYes


  • Histone deacetylase inhibitors
  • Melanoma
  • Trichostatin A
  • p53

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Plant Science
  • Developmental Biology
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Melanoma cell lines are susceptible to histone deacetylase inhibitor TSA provoked cell cycle arrest and apoptosis'. Together they form a unique fingerprint.

Cite this