A new selective AKT pharmacological inhibitor reduces resistance to chemotherapeutic drugs, TRAIL, all-trans-retinoic acid, and ionizing radiation of human leukemia cells

Withaferin A sensitizes TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of death receptor 5 and down-regulation of c-FLIP

“…Therefore, novel therapeutic strategies are necessary to overcome resistance of tumors to TRAIL. A burgeoning literature demonstrates that chemotherapeutic agents and ionizing radiation can sensitize TRAIL-induced cytotoxicity [33,34]. In this study, we show for the first time that Wit A effectively sensitizes human renal cancer cells, but not normal mesangial cells, to TRAIL-induced apoptosis through up-regulation of DR5 and down-regulation of c-FLIP, which are mediated by ROS signaling pathways.…”

Activation of FGFR1β signaling pathway promotes survival, migration and resistance to chemotherapy in acute myeloid leukemia cells

“…23 Furthermore, inhibition of Akt signaling has been shown to reduce chemoresistance in AML cells. [24][25][26] The particularly low constitutive activation of Akt in R81 cells and marked increase in phosphorylation upon stimulation may explain the observed strong proliferative response to FGF-2 in this cell line. Taken together, our results clearly show that FGF-2 signaling through FGFR1 can be physiologically relevant in subsets of AML.…”

Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia

“…179 In keeping with these findings and by exploiting the experimental system consisting of HL60AR cells, we demonstrated that one of these PIAs (1L-6-hydroxymethyl-chiro-inositol 2(R)-2-O-methyl-3-O-octadecylcarbonate) was able to restore sensitivity to chemotherapeutic drugs, ATRA and TRAIL. 180 Furthermore, we have tested two novel PIAs with improved metabolic stability and anticancer potential, D-3-deoxy-2-Omethyl-myo-inositol 1-((R)-2-methoxy-3-(octadecyloxy)propyl hydrogen phosphate and D-2,3-dideoxy-myo-inositol 1-((R)-2-methoxy-3-(octadecyloxy)propyl hydrogen phosphate (see compounds PIA5 and PIA6 in Castillo et al 178 ) on HL60AR cells. They were able to markedly increase sensitivity of HL60AR cells to etoposide or cytarabine at a concentration (5 mM), which was not toxic to human cord blood CD34 þ hematopoietic precursor cells.…”