Targeting FoxM1 transcription factor in T-cell acute lymphoblastic leukemia cell line.

Abstract

The Forkhead box protein M1 (FoxM1) is an important transcription factor having significant roles in various cellular events. FoxM1 overexpression has been reported to be related with many types of cancer. However, it is not known whether it contributes to oncogenesis of acute lymphoblastic leukemia. Siomycin A, a thiazol antibiotic, is known to inhibit FoxM1 transcriptional activity. In this study, we aimed to determine gene expression levels of FoxM1 in Jurkat cells (T-cell acute lymphoblastic leukemia cell line) and therapeutic potential of targeting FoxM1 by siomycin A alone and in combination with dexamethasone which improves the survival of children with T-cell acute lymphoblastic leukemia (ALL). We also examined the molecular mechanisms of siomycin A and dexamethasone-induced cell death in Jurkat cells. We demonstrated that FoxM1 mRNA is highly expressed in Jurkat cells. Dexamethasone and siomycin A caused a significant reduction in gene expression levels of FoxM1 in Jurkat cells. Targeting FoxM1 by siomycin A and dexamethasone caused a significant decrease in T-ALL cell line proliferation through induction of G1 cell cycle arrest. All these findings suggest a possible role of FoxM1 in T-cell ALL pathogenesis and represent FoxM1 as an attractive target for T-cell ALL therapy.

• Authors: Özlem Tüfekçi, Melis Kartal Yandım, Hale Ören, Gülersu İrken, Yusuf Baran
• Journal: Leukemia research (Leuk Res) Vol. 39 Issue 3 Pg. 342-7 (Mar 2015) ISSN: 1873-5835 [Electronic] England
• PMID: 25557384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Hormonal
• FOXM1 protein, human
• Forkhead Box Protein M1
• Forkhead Transcription Factors
• Peptides
• RNA, Messenger
• siomycin
• Dexamethasone

Topics

• Antineoplastic Agents, Hormonal (pharmacology)
• Antineoplastic Combined Chemotherapy Protocols
• Apoptosis (drug effects)
• Blotting, Western
• Cell Cycle (drug effects)
• Cell Proliferation (drug effects)
• Dexamethasone (pharmacology)
• Forkhead Box Protein M1
• Forkhead Transcription Factors (antagonists & inhibitors, genetics, metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Peptides (pharmacology)
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, metabolism, pathology)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Cells, Cultured