A novel histone deacetylase inhibitor augments tamoxifen-mediated attenuation of breast carcinoma growth Academic Article uri icon

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.

authors

  • Restall, Christina
  • Doherty, Judy
  • Liu, Hong Bin
  • Genovese, Rosemary
  • Paiman, Lisa
  • Byron, Keith A
  • Anderson, Robin L
  • Dear, Anthony E

publication date

  • July 15, 2009