A novel histone deacetylase inhibitor augments tamoxifen-mediated attenuation of breast carcinoma growth

Int J Cancer. 2009 Jul 15;125(2):483-7. doi: 10.1002/ijc.24350.

Abstract

Earlier we generated novel derivatives of the hydroxamate-based histone deacetylase inhibitor (HDACi), Oxamflatin (Ox), which demonstrate considerable HDACi activity. Here the effects of one such derivative, Metacept-1 (MCT-1), alone or in combination with tamoxifen on mammary tumour growth have been assessed in a syngeneic orthotopic model. MCT-1 alone resulted in a trend towards inhibition of growth of 4T1.2 mammary tumours. Since the combination of MCT-1 and tamoxifen up-regulates estrogen receptor expression in 4T1.2 cells in vitro, we tested this combination and found a significant reduction in primary tumour growth over tamoxifen treatment alone. Taken together, these observations suggest that the novel HDACi MCT-1 may warrant further exploration in the treatment of estrogen receptor positive breast carcinoma, particularly when used in combination with conventional agents such as tamoxifen.

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Base Sequence
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • DNA Primers
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology*
  • Estrogen Receptor alpha / metabolism
  • Histone Deacetylase Inhibitors*
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Tamoxifen / pharmacology*

Substances

  • Antineoplastic Agents, Hormonal
  • DNA Primers
  • Enzyme Inhibitors
  • Estrogen Receptor alpha
  • Histone Deacetylase Inhibitors
  • Tamoxifen