Effects of calpain inhibitors - KR-180 - and - KR-185 - in 3T3 preadipocytes and several cancer cell lines
Calpains are calcium dependent, non-lysosomal cysteine proteases. They are expressed ubiquitously in mammals and many other organisms. Excessive activities of calpain have been associated with various diseases, including Alzheimer’s disease (AD), cancer, neurological injury, ischemia/reperfusion injury, atherosclerosis, and diabetes and cataract formation. Thus calpain inhibitors are used to treat these diseases. Newly synthesized proprietary compounds KR-180 and KR-185 were investigated for its cytotoxicity in this preliminary study. We tested cell viability after treatment of cells for 24 h with KR-180 at 1 mM 100 μM, 10 uM, 1 uM, 100 nM, 10 nM. Cell viability was measured by the alamarBlue colorimetric assay. For 3T3-L1 cells, the KR-180 treatment at 1 mM reduced cell viability by 80%, while treatment at lower KR-180 concentrations did not affect 3T3-L1 viability. The similar effect was observed for lung cancer cell line A549 where a significant reduction (about 40%) in cell viability was seen at the 1 mM dose. For colon cancer cell line (SW620) and prostate cancer cell line (PC3), all tested KR-180 concentrations did not cause any significant reduction in viability. In summary, preliminary results suggest that the compound has low cytotoxicity, since it could cause cell death at high concentration 100 μM or higher. Calpine activity decreased significantly with increase in dose of KR-180 in 3T3 L1 Preadipocytes. 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.
"Effects of calpain inhibitors - KR-180 - and - KR-185 - in 3T3 preadipocytes and several cancer cell lines"
ETD Collection for Tennessee State University.