Influence of new calpain inhibitors KR-185 and KR-161 on some biochemical parameters in cancer and 3T3-L1 preadipocytes
Several studies have notably highlighted the involvement of calpains in the processes essential for cancer development and cell cycle progression, including; cell transformation, migration and tumor invasion, angiogenesis, apoptosis/survival. As a result, calpains are considered by several researchers as potential anti-cancer targets. So many calpain inhibitors have been synthesized with or without specificity for different isoforms of calpain. In this study, we investigated the effect of calpain inhibitors KR-185 and KR-161 on some biochemical parameters. These parameters are cell viability, calpain activity, antioxidant potentials (GSH assay) and Caspase-9 expression levels, which are essential for cancer development in humans. In this study, A549 lung cancer cells, HeLa cells, BT549 breast cancer cells and 3T3-L1 preadipocytes were exposed to either the same or different doses of the newly synthesized calpain inhibitors KR-185 and KR-161 after establishing a safe and working dose of 5, 10, 15, 20 and 25 μM or 0, 10, 20 30, 50 and 70 μM depending on the cell line. The effect of both calpain inhibitors on cytotoxicity was minimal even at high concentration. In comparison, the results obtained revealed that KR-161 are more specific than KR-185 for a wider range of calpain in cancer and fat cells. Reduction in calpain activity was observed in all cell lines when treated with KR-161 for 24 hours unlike KR-185 which was specific to only A549 lung cancer cells and BT549 breast cancer cells. Both calpain inhibitors were observed to reduce the endogenous glutathione levels of almost all cell lines but not below the normal physiological level (10 μM). KR-185 decreased the expression of caspase-9 in A549 lung cancer cells, HeLa cells and BT549 breast cancer cells. Its effect on the expression of caspase-9 in 3T3-L1 preadipocytes could not be assayed for due to the specificity of the kit for human caspase-9 not cells from mice.
"Influence of new calpain inhibitors KR-185 and KR-161 on some biochemical parameters in cancer and 3T3-L1 preadipocytes"
ETD Collection for Tennessee State University.