Decades of comprehensive research have resulted in a better understanding of the crucial role of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling in different types of leukemia whereby it strongly influences the growth and survival of cancerous cells. Recently, small-molecule inhibitors have been introduced as targeted therapies that are more tolerable than conventional antineoplastic drugs for leukemia. The growth inhibition assays were performed to assess the effectiveness of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway inhibitors like everolimus, torkinib and phosphokinase inhibitor 402 in leukemia cell lines. The cell cycle profiles, protein kinase B and S6 phosphorylations were assessed by flow cytometry. We also screened the expression of 96 cancer-associated long non-coding RNAs upon phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway inhibition. Compared to untreated cells, the smallmolecule inhibitors treated cells showed reduced viability. Phosphokinase inhibitor 402, a dual pathway inhibitor was most effective in all cell lines (56.6 %, 32.5 % and 11.4 % in Jurkat, HL-60 and K562 cells, respectively). In addition, treatment with this resulted to shift the cells to the G1 phase from the S1 phase (Jurkat, G1: 12.2 %, S1: 4.9 %; HL-60, G1: 38.4 %, S1: 44.4 %; K562 G1: 14.4 %, S1: 15.7 %), more effectively than everolimus or torkinib. It was observed that when this inhibitor was used, the long non-coding RNAs retinal non-coding RNA 3 (3-fold) and highly up-regulated in liver cancer (2-fold) levels were significantly elevated whereas antisense non-coding ribonucleic acid in the INK4 locus and zinc finger homeobox 2 were significantly decreased by at least 25 %. Our findings revealed that dualspecificity inhibitors are more potent than single-specificity inhibitors. Hence, dual-targeted therapy may be a promising therapeutic option for leukemia. In addition, long non-coding RNAs may play a key role in drug resistance and could be a potential novel therapeutic target.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.