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.
Guirgis
Adel A
AA
Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute (GEBRI), Menoufiya University, Egypt.
Zahran
Magdy A H
MA
Mohamed
Amr S
AS
Talaat
Roba M
RM
Abdou
Bishoy Y
BY
Agwa
Hussein S
HS
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009368:Neoplasm Transplantation; D009569:Nitric Oxide / Q000378:metabolism; D013792:Thalidomide / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D013859:Thiocarbamates / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D013859:Thiocarbamates; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D013792:Thalidomide; D007770:L-Lactate Dehydrogenase