A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells.

Abstract

Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on human leukemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to investigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.

• Authors: Zuo-Fu Peng, Lin-Xiang Lan, Fang Zhao, Jing Li, Qiang Tan, Han-Wei Yin, Hui-Hui Zeng
• Journal: Journal of Zhejiang University. Science. B (J Zhejiang Univ Sci B) Vol. 9 Issue 1 Pg. 16-21 (Jan 2008) ISSN: 1673-1581 [Print] China
• PMID: 18196608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• (1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone))ethane
• Bridged Bicyclo Compounds, Heterocyclic
• Enzyme Inhibitors
• Organoselenium Compounds
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Thioredoxin-Disulfide Reductase

Topics

• Apoptosis (drug effects)
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Cell Proliferation (drug effects)
• Enzyme Inhibitors (pharmacology)
• HL-60 Cells
• Humans
• K562 Cells
• Organoselenium Compounds (pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (physiology)
• Thioredoxin-Disulfide Reductase (antagonists & inhibitors)
• bcl-2-Associated X Protein (physiology)