title: A novel histone deacetylase inhibitor augments tamoxifen-mediated attenuation of breast carcinoma growth.
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.affiliation: Cancer Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
authors.forename: Christina
authors.initials: C
authors.lastname: Restall
authors.forename: Judy
authors.initials: J
authors.lastname: Doherty
authors.forename: Hong Bin
authors.initials: HB
authors.lastname: Liu
authors.forename: Rosemary
authors.initials: R
authors.lastname: Genovese
authors.forename: Lisa
authors.initials: L
authors.lastname: Paiman
authors.forename: Keith A
authors.initials: KA
authors.lastname: Byron
authors.forename: Robin L
authors.initials: RL
authors.lastname: Anderson
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Dear