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A novel histone deacetylase inhibitor augments tamoxifen‐mediated attenuation of breast carcinoma growth
Author(s) -
Restall Christina,
Doherty Judy,
Liu Hong Bin,
Genovese Rosemary,
Paiman Lisa,
Byron Keith A.,
Anderson Robin L.,
Dear Anthony E.
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24350
Subject(s) - tamoxifen , cancer research , histone deacetylase , estrogen receptor , antiestrogen , growth inhibition , breast cancer , estrogen , breast carcinoma , mammary gland , medicine , in vitro , biology , pharmacology , endocrinology , cancer , histone , biochemistry , gene
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. © 2009 UICC