期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 409, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2020.115299
关键词
Arsenic Trioxide; Acute Promyelocytic Leukemia; Adverse Effect; Metabolism; Methylated Arsenicals
资金
- National Natural Science Foundation of China [82003875, 81673521, 81872942, 81970133]
- China Postdoctoral Science Foundation [233618]
- Postdoctoral Advanced Programs of Zhejiang Province [ZJ2020154]
Arsenic trioxide (ATO) has a long history and it is recognized as both poison and drug for more than two thousand years. Since the establishment of ATO as a frontline therapeutic agent for acute promyelocytic leukemia (APL), the survival of APL patients have been greatly improved and APL is turned from highly fatal to highly curable disease. Mechanistically, ATO can induce PML/RAR alpha fusion protein degradation, causing APL cell differentiation and apoptosis. On the other hand, the side effects such as differentiation syndrome, cardiac conduction abnormalities and liver toxicity are often observed during the ATO treatment of APL in clinic. It is likely that the therapeutic and adverse effects of ATO is probably associated with its distinct pattern of metabolism and direct or indirect effects on different organs. In this review, we provided a comprehensive and indepth elaboration of the cytotoxic mechanisms of ATO and its methylated metabolites based on in vivo or in vitro studies, trying to clarify the importance of achieving balance between the toxicity and anti-leukemic activity of ATO in APL treatment.
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