Arsenic oxide targets stem cell marker CD133/prominin-1 in gallbladder carcinoma.

Abstract	CD133+ tumor cells are responsible for the initiation, propagation and recurrence of tumors, which raises the question of how to effectively target CD133+ tumor cells. Arsenic trioxide (As2O3) has considerable efficacy in treating solid tumors with induction of apoptosis. Here, we found that purified CD133+ gallbladder carcinoma cells are highly resistant to conventional chemotherapy. However, As2O3 effectively induces CD133+ gallbladder carcinoma cells apoptosis. Treatment with As2O3 reduces CD133 expression at transcriptional levels. Furthermore, the ectopic expression of CD133 attenuated the apoptotic effect of As2O3 on cells through activation of AKT signaling pathways. Collectively, As2O3 effectively targets CD133 in gallbladder carcinoma, providing a new mechanism of As2O3-induced cell apoptosis and a better understanding of drug resistance in gallbladder carcinoma.
Authors	Zhilong Ai, Hongtao Pan, Tao Suo, Chentao Lv, Yueqi Wang, Saixiong Tong, Houbao Liu
Journal	Cancer letters (Cancer Lett) Vol. 310 Issue 2 Pg. 181-7 (Nov 28 2011) ISSN: 1872-7980 [Electronic] Ireland
PMID	21788103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Chemical References	AC133 Antigen Antigens, CD Antineoplastic Agents Arsenicals Glycoproteins Oxides PROM1 protein, human Peptides RNA, Messenger Proto-Oncogene Proteins c-akt Arsenic Trioxide
Topics	AC133 Antigen Antigens, CD (biosynthesis, genetics) Antineoplastic Agents (pharmacology) Apoptosis (drug effects, physiology) Arsenic Trioxide Arsenicals (pharmacology) Cell Line, Tumor Down-Regulation (drug effects) Drug Resistance, Neoplasm Gallbladder Neoplasms (drug therapy, immunology, pathology) Glycoproteins (biosynthesis, genetics) Humans Neoplastic Stem Cells (drug effects, immunology, pathology) Oxides (pharmacology) Peptides (genetics) Plasmids (genetics) Proto-Oncogene Proteins c-akt (metabolism) RNA, Messenger (biosynthesis, genetics) Signal Transduction Transfection

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