nsc-4347 and Precursor-B-Cell-Lymphoblastic-Leukemia-Lymphoma

nsc-4347 has been researched along with Precursor-B-Cell-Lymphoblastic-Leukemia-Lymphoma* in 1 studies

Other Studies

1 other study(ies) available for nsc-4347 and Precursor-B-Cell-Lymphoblastic-Leukemia-Lymphoma

ArticleYear
Piperlongumine inhibits the proliferation and survival of B-cell acute lymphoblastic leukemia cell lines irrespective of glucocorticoid resistance.
    Biochemical and biophysical research communications, 2014, Sep-26, Volume: 452, Issue:3

    Piperlongumine (PL), a pepper plant alkaloid from Piper longum, has anti-inflammatory and anti-cancer properties. PL selectively kills both solid and hematologic cancer cells, but not normal counterparts. Here we evaluated the effect of PL on the proliferation and survival of B-cell acute lymphoblastic leukemia (B-ALL), including glucocorticoid (GC)-resistant B-ALL. Regardless of GC-resistance, PL inhibited the proliferation of all B-ALL cell lines, but not normal B cells, in a dose- and time-dependent manner and induced apoptosis via elevation of ROS. Interestingly, PL did not sensitize most of B-ALL cell lines to dexamethasone (DEX). Only UoC-B1 exhibited a weak synergistic effect between PL and DEX. All B-ALL cell lines tested exhibited constitutive activation of multiple transcription factors (TFs), including AP-1, MYC, NF-κB, SP1, STAT1, STAT3, STAT6 and YY1. Treatment of the B-ALL cells with PL significantly downregulated these TFs and modulated their target genes. While activation of AURKB, BIRC5, E2F1, and MYB mRNA levels were significantly downregulated by PL, but SOX4 and XBP levels were increased by PL. Intriguingly, PL also increased the expression of p21 in B-ALL cells through a p53-independent mechanism. Given that these TFs and their target genes play critical roles in a variety of hematological malignancies, our findings provide a strong preclinical rationale for considering PL as a new therapeutic agent for the treatment of B-cell malignancies, including B-ALL and GC-resistant B-ALL.

    Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Aurora Kinase B; Cell Line, Tumor; Cell Proliferation; Dexamethasone; Dioxolanes; DNA-Binding Proteins; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; E2F1 Transcription Factor; Gene Expression Regulation, Leukemic; Glucocorticoids; Humans; Inhibitor of Apoptosis Proteins; Neoplasm Proteins; Piper; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Proto-Oncogene Proteins c-myb; Regulatory Factor X Transcription Factors; rho GTP-Binding Proteins; Signal Transduction; SOXC Transcription Factors; Survivin; Transcription Factors

2014