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