monensin and Uterine-Cervical-Neoplasms

Previously, we showed that monensin, Na+ ionophore, potently inhibited the growth of acute myelogenous leukemia and lymphoma cells. Here, we demonstrate that monensin inhibited the proliferation of solid tumor cells with IC50 of about 2.5 micro M. Monensin induced a G1 or a G2-M phase arrest in these cells. When we examined the effects of this drug on SNU-C1 cells, monensin decreased the levels of CDK2, CDK4, CDK6, cyclin D1 and cyclin A proteins. While p27 was increased by monensin, p21 was not. In addition, monensin markedly enhanced the binding of p27 with CDK2, CDK4 and CDK6. Furthermore, the activities of CDK2-, CDK4- and CDK6-associated kinase were reduced in association with hypophosphorylation of Rb protein. Monensin also induced apoptosis in solid tumor cells. Apoptotic process of SNU-C1 cells was associated with the changes of Bax, caspase-3 and mitochondria transmembrane potential (deltapsim). Taken together, these results demonstrated for the first time that monensin inhibited the growth of solid tumor cells, especially SNU-C1 cells, via cell cycle arrest and apoptosis.

Topics: Adenocarcinoma; Apoptosis; bcl-2-Associated X Protein; Breast Neoplasms; Caspase 3; Caspases; CDC2-CDC28 Kinases; Cell Cycle; Cell Cycle Proteins; Cell Division; Colonic Neoplasms; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinases; Drug Screening Assays, Antitumor; Female; HeLa Cells; Humans; Inhibitory Concentration 50; Intracellular Membranes; Ionophores; Membrane Potentials; Mitochondria; Monensin; Neoplasm Proteins; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Retinoblastoma Protein; Sodium; Tumor Cells, Cultured; Tumor Suppressor Proteins; Uterine Cervical Neoplasms