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

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.
AuthorsZhilong Ai, Hongtao Pan, Tao Suo, Chentao Lv, Yueqi Wang, Saixiong Tong, Houbao Liu
JournalCancer letters (Cancer Lett) Vol. 310 Issue 2 Pg. 181-7 (Nov 28 2011) ISSN: 1872-7980 [Electronic] Ireland
PMID21788103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • AC133 antigen
  • Antigens, CD
  • Antineoplastic Agents
  • Arsenicals
  • Glycoproteins
  • Oxides
  • Peptides
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • arsenic trioxide
  • Antigens, CD (biosynthesis, genetics)
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects, physiology)
  • 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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