The anti-leukemic effect of a novel histone deacetylase inhibitor MCT-1 and 5-aza-cytidine involves augmentation of Nur77 and inhibition of MMP-9 expression

Int J Oncol. 2009 Feb;34(2):573-9.


A combination of demethylating agents and histone deacetylase inhibitors (HDACi) has been proposed as a novel therapy in leukemia and myelodysplasia. In HL-60 cells azacytidine (AZA) and Metacept-1 (MCT-1), a novel HDACi augmented inhibition of cell growth and increased apoptosis. In identifying a molecular mechanism responsible for these effects MCT-1 alone and in combination with AZA induced p15INK4b, p21WAF1/CIP1 and Caspase-3 whilst attenuating Bcl-XL expression. Interestingly, MCT-1 in combination with AZA significantly induced the recently identified suppressor of leukemogenesis Nur77 and attenuated AZA-induced MMP-9 expression. The combination of MCT-1 and AZA is more effective in inhibiting leukemic cell growth and induction of apoptosis. Regulation of a recently identified tumour suppressor gene together with cell cycle, apoptosis and matrix degrading proteases may underpin the molecular mechanism responsible for these effects.

MeSH terms

  • Antimetabolites, Antineoplastic / therapeutic use*
  • Apoptosis / drug effects
  • Azacitidine / therapeutic use*
  • Cyclin-Dependent Kinase Inhibitor p15 / genetics
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • HL-60 Cells / drug effects
  • Histone Deacetylase Inhibitors*
  • Humans
  • Hydroxamic Acids / therapeutic use*
  • Leukemia / drug therapy*
  • Matrix Metalloproteinase 9 / genetics*
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / isolation & purification
  • Receptors, Steroid / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / therapeutic use*


  • Antimetabolites, Antineoplastic
  • CDKN2B protein, human
  • Cyclin-Dependent Kinase Inhibitor p15
  • DNA-Binding Proteins
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Steroid
  • Sulfonamides
  • metacept-1
  • Matrix Metalloproteinase 9
  • Azacitidine