Title | Novel mechanism of ethaselen in poorly differentiated colorectal RKO cell growth inhibition: Simultaneous regulation of TrxR transcription, expression and enzyme activity |
Authors | Yin, Hanwei Li, Jing Xiong, Kun Wang, Lihui Wang, Tianyu Tan, Qiang Fu, Jianing Ren, Xiaoyuan Zeng, Huihui |
Affiliation | Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Beijing 100191, Peoples R China. Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. Peking Univ, Coll Life Sci, Beijing 100075, Peoples R China. Peking Univ First Hosp, Beijing 100034, Peoples R China. Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Mailbox 74, Beijing 100191, Peoples R China. |
Keywords | Thioredoxin reductase Ethaselen RKO cell LoVo cell Poorly differentiated Wnt/beta-catenin THIOREDOXIN REDUCTASE INHIBITOR CANCER STEM-CELLS BETA-CATENIN PROGENITOR CELLS TGF-BETA IN-VITRO APOPTOSIS PROTEIN GENE LINES |
Issue Date | 2011 |
Publisher | differentiation |
Citation | DIFFERENTIATION.2011,81,(1),49-56. |
Abstract | Thioredoxin reductase (TrxR) is a ubiquitous intracellular redox enzyme that regulates tumor growth and proliferation in various cancer cells. Ethaselen (1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]-ethane), a novel anticancer agent, is designed to target mammalian TrxR1 with the aims of cancer growth inhibition and TrxR inactivation. In this study, we demonstrated that ethaselen significantly inhibits cell growth in the poorly differentiated colorectal RKO cell line, and simultaneously downregulates mammalian TrxR1 mRNA transcript levels, protein expression and enzyme activity, which differs from its actions in moderately differentiated colorectal LoVo cells. Ethaselen's significant abatement of the Wnt/beta-catenin cell differentiation-related signaling pathway was also observed in RKO cells; this apparently leads to its strong inhibitory effect on cell growth and TrxR1 activity in this cell line. These results suggest that ethaselen has a novel mechanism affecting cell growth in the poorly differentiated RKO colorectal cell line. (c) 2010 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved. |
URI | http://hdl.handle.net/20.500.11897/156698 |
ISSN | 0301-4681 |
DOI | 10.1016/j.diff.2010.09.180 |
Indexed | SCI(E) PubMed |
Appears in Collections: | 生命科学学院 第一医院 天然药物与仿生药物国家重点实验室 |