Nucleostemin knocking-down causes cell cycle arrest and apoptosis in human T-cell acute lymphoblastic leukemia MOLT-4 cells via p53 and p21Waf1/Cip1 up-regulation

Abstract

Objectives: Nucleostemin (NS), a recently discovered nucleolar protein, is essential for maintaining self-renewal and proliferation of embryonic and adult stem cells as well as cancerous cells. The aim of this study was to determine biological function of NS in MOLT-4 cells as a human T-cell acute lymphocytic leukemia (T-ALL) model.

Methods: Efficacy of a specific small interference RNA on NS depletion was studied by quantitative polymerase chain reaction and western blotting. The growth rate and viability were analyzed by trypan blue exclusion test. Fluorescent microscopy was used for detecting apoptosis. Cell cycle and apoptosis were mechanistically studied by flow cytometry and western blotting.

Results: Knockdown of NS inhibited proliferation, arrested the cell cycle, and induced apoptosis through p53 and p21(Waf1/Cip1) pathways in MOLT-4 cells.

Discussion: These findings demonstrate critical roles of NS in MOLT-4 cells and may implicate on its therapeutic potential in this human T-ALL model.

Keywords: Acute lymphoblastic leukemia; Apoptosis; MOLT-4; Nucleostemin; p21Waf1/Cip1 (Waf1/cip1); p53.