title: The steroidal Na+/K+ ATPase inhibitor 3-[(R)-3-pyrrolidinyl]oxime derivative (3-R-POD) induces potent pro-apoptotic responses in colonic tumor cells.
abstract: Recently, potent anticancer actions of the steroidal Na(+)/K(+) ATPase inhibitor 3-[(R)-3-pyrrolidinyl]oxime derivative 3 (3-R-POD) have been reported for multiple cell lines, including prostate and lung cancer cells. In the present study, the anticancer action of 3-R-POD was addressed in colonic tumor cells. Treatment of Caco2 colonic tumor cells with increasing concentrations of 3-R-POD induced potent, dose-dependent inhibition of cell growth as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the APOpercentage apoptosis assay revealed significant pro-apoptotic responses, suggesting that the anticancer activity of this steroidal Na(+)/K(+) ATPase inhibitor in colonic tumors takes places mainly through the induction of strong pro-apoptotic effects. Focussing on the molecular mechanism that may regulate these interactions, 3-R-POD was shown to induce significant early actin re-organization and late Protein Kinase B (AKT) de-phosphorylation. Finally, the 3-R-POD-induced inhibition of cell growth and early actin reorganization in colonic cancer cells remained unchanged when cells were pre-treated with pertussis toxin, thus excluding possible interactions of this inhibitor with G-coupled receptors. These results indicate that 3-R-POD induces potent pro-apoptotic responses in colonic tumor cells governed by actin re-organization and inhibition of AKT pro-survival signaling.
authors.affiliation: Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia salkahtani@ksu.edu.sa.
authors.forename: Saad Hussin
authors.initials: SH
authors.lastname: Alkahtani
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation; D010091:Oximes / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D010091:Oximes; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Akt; Na+/K+ ATPase inhibitor; actin; apoptosis; colon tumor