TY - JOUR T1 - The Steroidal Na<sup>+</sup>/K<sup>+</sup> ATPase Inhibitor 3-[(<em>R</em>)-3-Pyrrolidinyl]oxime Derivative (3-R-POD) Induces Potent Pro-Apoptotic Responses in Colonic Tumor Cells JF - Anticancer Research JO - Anticancer Res SP - 2967 LP - 2971 VL - 34 IS - 6 AU - SAAD HUSSIN ALKAHTANI Y1 - 2014/06/01 UR - http://ar.iiarjournals.org/content/34/6/2967.abstract N2 - 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. ER -