Figure 4

Oxamate and amino oxyacetate (AOA) are selectively toxic to MDA-MB-231 transformed human mammary epithelial cells (HMEC) and suppress the growth of established breast tumour xenografts in vivo. Growth inhibition studies were performed as described. MDA-MB-231 cells or HMEC were cultured in identical media for 48 hours in the absence or presence of the indicated concentrations of (a) oxamate or (b) AOA. Cells were exposed to trypan blue and enumerated using light microscopy (dashed line indicates percentage control at time of plating). MDA-MB-231 cells at a concentration of 2.5 × 10⁴ were plated on 6 cm dishes containing Dulbecco's Modified Eagle's Medium (DMEM) with 0.6% agar in the absence or presence of the indicated concentrations of (c) oxamate or (d) AOA. Cells were fed with 0.2% agar in media containing oxamate every three to five days. After 28 days, soft agar colonies were enumerated and expressed as a percentage of control. MDA-MB-231 xenografts were initiated as described. Tumours were measured daily using blunt end Vernier calipers, and mice with established tumours (130 to 190 mg) were blindly randomised into either PBS control (●) or treatment (○) groups. Experimental mice were weighed, and given daily intraperitoneal injections of either PBS or (e) 15 mg oxamate or (f) 0.2 mg AOA. Data are plotted as the mean ± standard deviation.