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Balance between the toxicity and anticancer activity of arsenic trioxide in treatment of acute promyelocytic leukemia.

Abstract：

: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/RARα 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 in-depth 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.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Wang QQ,Hua HY,Naranmandura H,Zhu HH

doi

10.1016/j.taap.2020.115299

subject

Has Abstract

pub_date

2020-12-15 00:00:00

pages

115299

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(20)30425-7

journal_volume

409

pub_type

杂志文章,评审

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