Arsenic trioxide (As₂O₃) inhibits murine WEHI-3 leukemia in BALB/c mice in vivo.

Abstract

Arsenic trioxide (As₂O₃) is used clinically to treat acute promyelocytic leukemia (APL) and has activity in vitro for induction of apoptosis in several solid tumor cell lines. To investigate the potential therapeutic application of As₂O₃ for leukemia, we analyzed the effects of As₂O₃ on the WEHI-3 cells-induced orthotopic leukemia animal model in vivo in this study. We established the WEHI-3 cells leukemia mice through the injection of murine WEHI-3 cells into BALB/c mice, and they were then treated with As₂O₃ (0.9 and 4.5 mg kg⁻¹ ; p.o.) and/or combined with all-trans-retinoic acid (ATRA), (30 mg kg⁻¹ ; i.p.). The results indicated that (1) As₂O₃ alone or As₂O₃ combined with ATRA promoted the total survival rate of leukemia mice and these effects are dose-dependent; (2) As₂O₃ did not affect the body weight but decreased the spleen weight; however, it did not affect liver weight; (3) As₂O₃ alone or As₂O₃ combined with ATRA increased the levels of CD3 and CD19, indicating that the differentiation of T and B cells were promoted; and (4) As₂O₃ alone or As₂O₃ combined with ATRA did not change the levels of Mac-3 and CD11b markers, indicating that the differentiation of the precursor of macrophage were not inhibited. Based on these observations, As₂O₃ alone or As₂O₃ combined with ATRA have efficacious antileukemia activity in WEHI-3 cells leukemia in vivo.

• Authors: Tung-Yuan Lai, Jen-Jyh Lin, Wen-Wen Huang, Shu-Chu Kuo, Yen-Fang Wen, I-Cheng Lai, Chin-Chung Lin, Jai-Sing Yang, Jing-Gung Chung
• Journal: Environmental toxicology (Environ Toxicol) Vol. 27 Issue 6 Pg. 364-71 (May 2012) ISSN: 1522-7278 [Electronic] United States
• PMID: 20886602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Wiley Periodicals, Inc.

Chemical References

• Antigens, Differentiation
• Arsenicals
• Oxides
• monocyte-macrophage differentiation antigen
• Tretinoin
• Arsenic Trioxide

Topics

• Animals
• Antigens, Differentiation (metabolism)
• Arsenic Trioxide
• Arsenicals (administration & dosage, pharmacology)
• B-Lymphocytes (cytology)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Leukemia (drug therapy, pathology)
• Leukemia, Experimental (drug therapy, pathology)
• Macrophages (cytology)
• Male
• Mice
• Mice, Inbred BALB C
• Oxides (administration & dosage, pharmacology)
• Spleen (drug effects, pathology)
• Tretinoin (administration & dosage, pharmacology)