NAT2 activity increases cytotoxicity of anthracycline antibiotics and HDAC inhibitors

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-03-13 DOI:10.1016/j.bbadis.2025.167755

Natallia Rameika , Ioanna Tsiara , Xiaonan Zhang , Wawrzyniec Haberek , Verónica Rendo , Snehangshu Kundu , Mario S.P. Correia , Ivaylo Stoimenov , Daniel Globisch , Tobias Sjöblom

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引用次数: 0

Abstract

The Arylamine-N-acetyltransferase-2 (NAT2) enzyme is involved in metabolism of commonly used drugs driving differences in efficacy and tolerability of treatments. To bridge the current knowledge gap on metabolism of cytotoxic drugs by NAT2, and identify anticancer agents whose effects depend on NAT2 activity, we assessed 147 clinically used drugs. Hit compounds were evaluated for metabolic conversion by acetylation in presence of recombinant NAT2. Among those 147 drugs we found doxorubicin, daunorubicin, epirubicin, valrubicin, teniposide, afatinib, carmustine, vincristine, panobinostat, and vorinostat to have increased toxicity to cancer cells expressing the rapid NAT2 allele. Additionally, we report NAT2-mediated acetylation of idarubicin, daunorubicin, doxorubicin, vorinostat, and CUDC-101. These findings have implications for pharmacogenomics and cancer precision medicine using conventional chemotherapeutic drugs, as improving their efficacy and safety may affect >4 million cancer patients worldwide that receive these drugs as standard of care.

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.