Effect of thalidomide dithiocarbamate analogs on the intercellular adhesion molecule-1 expression.

Thalidomide has been reported to have anti-angiogenic and antimetastatic effects. Intercellular adhesion molecule-1 (ICAM-1) was shown to be involved in monocyte adherence to epithelial cells and cancer cell invasion. Novel thalidomide dithiocarbamate analogs (containing 2 sulfur atoms) were designed and synthesized as potential anti-tumor agents. The aim of this work is to investigate their anti-tumor effect against transplantable experimental tumor, Ehrlich ascites carcinoma (EAC), in mice by studying the changes in cell's biochemical profile, the expression of ICAM-1 and nitric oxide (NO) and their association with tumor burden. As shown in our results, treatment of solid tumor-bearing mice with thalidomide 1 resulted in a significant reduction in tumor volume with 75.4% inhibition, a significant decrease in lactate dehydrogenase (LDH), ICAM-1 expression and NO. Thalidomide dithiocarbamate analogs 2 and 3 exhibited a potent effect to reduce the volume of solid tumor with 96.7% and 96.5% inhibition, respectively, a significant ability to increase the albumin, alanine aminotransferase (ALT) and glucose levels and to diminish LDH, ICAM-1 expression and NO. Thalidomide dithiocarbamate analog 3 has more potent anti-tumor activity as compared with thalidomide 1 or its dithiocarbamate analog 2. Taken together, our study improved that the dithiocarbamate analogs 2 and 3 are more potent anti-tumor agents with more pronounced effect than thalidomide 1 itself.