Biotransformation of arsenic trioxide by AS3MT favors eradication of acute promyelocytic leukemia : revealing the hidden facts
Arsenic trioxide (ATO) is one of the most effective drugs for treatment of acute promyelocytic leukemia (APL). It could specifically target the PML/RARα fusion oncoprotein stability and induces APL cell differentiation as well as apoptosis. Although many studies have been conducted to document the anticancer effects and mechanism of ATO, there is little information about the association between biotransformation of ATO to active arsenic metabolites and APL therapy. Generally, ATO can be rapidly converted into trivalent methylated metabolites by arsenic (+3 oxidation state) methyltransferase (AS3MT) mostly in liver and redistributed to bloodstream of APL patients who receiving ATO treatment, thereby leading to a balance between cytotoxicity and differentiation, which is proposed to be the key event in successful treatment of APL. In this review, we comprehensively discussed possible roles of AS3MT and methylated arsenic metabolites in APL therapy, so as to reveal the association between individual differences of AS3MT expression and activity with the therapeutic efficacy of ATO in APL patients.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
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| Enthalten in: |
Drug metabolism reviews - 52(2020), 3 vom: 18. Aug., Seite 425-437 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Maimaitiyiming, Yasen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.06.2021 Date Revised 30.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/03602532.2020.1791173 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM312538502 |
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| 520 | |a Arsenic trioxide (ATO) is one of the most effective drugs for treatment of acute promyelocytic leukemia (APL). It could specifically target the PML/RARα fusion oncoprotein stability and induces APL cell differentiation as well as apoptosis. Although many studies have been conducted to document the anticancer effects and mechanism of ATO, there is little information about the association between biotransformation of ATO to active arsenic metabolites and APL therapy. Generally, ATO can be rapidly converted into trivalent methylated metabolites by arsenic (+3 oxidation state) methyltransferase (AS3MT) mostly in liver and redistributed to bloodstream of APL patients who receiving ATO treatment, thereby leading to a balance between cytotoxicity and differentiation, which is proposed to be the key event in successful treatment of APL. In this review, we comprehensively discussed possible roles of AS3MT and methylated arsenic metabolites in APL therapy, so as to reveal the association between individual differences of AS3MT expression and activity with the therapeutic efficacy of ATO in APL patients | ||
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| 650 | 4 | |a arsenic trioxide | |
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