INHIBITION OF COLONY FORMATION IN AGAROSE OF METASTATIC HUMAN BREAST-CARCINOMA AND MELANOMA-CELLS BY SYNTHETIC GLYCOAMINE ANALOGS

We studied the influence of 10 synthetic glycoamine analogs on colony formation in 0.3 and 0.9% agarose by metastatic human breast carcinoma (MDA-MB-435) and melanoma (TXM-13) cells, Nine synthetic analogs sign ificantly inhibited the colony formation in 0.9% agarose of MDA-MB-435 human breast carcinoma cells; five compounds caused a 73-83% reductio n of colony formation, Seven synthetic glycoamines caused a significan t inhibition of colony formation in 0.9% agarose by TXM-13 melanoma ce lls with the inhibitory effect ranging from 71 to 87%, The 50% inhibit ion (I-50) doses and relative activity rank of the compounds were simi lar for both breast carcinoma and melanoma cell lines, The murine B16 melanoma cell aggregation assay was employed to elucidate the potentia l mechanism(s) of the inhibitory activity of synthetic glycoamines, Th e relative activity ranks of the compounds based on the independently determined I-50 doses for both cell aggregation and clonogenic growth assays were very similar for the four most active synthetic analogs an d clearly indicated the importance of hydrophobic amino acid in mediat ing the bioactivity of synthetic glycoamines, In both experimental sys tems (clonogenic growth in agarose and cell aggregation assay) the lea ding compound was N-(1-deoxy-D-fructos-1-yl)D-leucine (Fru-D-Leu) and the least active analog was N-(1-deoxy-D-fructos-1-yl)-glycine (Fru-Gl y), These results show that synthetic glycoamines may act by competing for specific carbohydrate-lectin interactions, particularly those inv olving beta-galactoside-specific lectins expressed on metastatic cells .