Cover image of the article: Induction of p21- and p27-mediated cell cycle arrest in Nalm-6 cells using pan-PI3K inhibitor (Buparlisib)

Image Credit:Koomesh

Induction of p21- and p27-mediated cell cycle arrest in Nalm-6 cells using pan-PI3K inhibitor (Buparlisib)

Authors

Ava Safaroghli-AzarAva Safaroghli-Azar ORCID, Mohammadreza Sadri, Davood Bashash,*
*Corresponding Author: Email: d.bashash@sbmu.ac.ir

Koomesh:Vol. 20, issue 4; 756-763
Published online:Mar 30, 2018
Article type:Research Article
Received:Nov 08, 2017
Accepted:Mar 01, 2018
How to Cite:Safaroghli-Azar A, Sadri M, Bashash D. Induction of p21- and p27-mediated cell cycle arrest in Nalm-6 cells using pan-PI3K inhibitor (Buparlisib). koomesh. 2018;20(4):e153023. doi:

Abstract

Introduction: In the era of targeted therapies, efforts are being made to identify the novel agents with strong anti-tumor activity in order to improve cure rates of human malignancies while reducing the toxic side effects of intensive regimens. Increasing number of genetic and cancer biology studies indicated a prominent role for the aberrant activation of PI3K/Akt pathway in not only the pathogenesis of acute lymphoblastic leukemia (ALL), but also in acquisition of chemo-resistant phenotype. In this study we aimed to assess the anti-proliferative effect of pan class I PI3K inhibitor, Buparlisib, on Nalm-6 cells. Materials and Methods: To evaluate whether inhibition of PI3K using Buparlisib could exert anti-proliferative effect in leukemic cells, Nalm-6 were subjected to different concentrations of the inhibitor and subsequent cell viability, cell count, cell cycle progression and transcriptional alteration of cell cycle-related genes were investigated. Results: Buparlisib not only decreased the number of viable inhibitor-treated cells in a concentration and time-dependent manner, but also reduced the survival rate of Nalm-6 cells. Furthermore, we found that the anti-proliferative effect of this inhibitor is mediated, at least partially, through induction of G1 arrest as a result of up-regulated p21 and p27 and down-regulated c.Myc expression level. Conclusion: The present study showed that Buparlisib decreased the proliferative capacity of Nalm-6 cells probably via reduction in DNA synthesize rate, induction of cell cycle arrest and alteration in the expression level of proliferative-related genes. The results suggest that PI3K inhibitors may be used as a promising therapeutic strategy for the treatment of ALL patients.

Highlights

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Copyright

© 2018, Author(s). This open-access article is available under the Creative Commons Attribution 4.0 (CC BY 4.0) International License (https://creativecommons.org/licenses/by/4.0/), which allows for unrestricted use, distribution, and reproduction in any medium, provided that the original work is properly cited.

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