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Arylamine N-acetyltransferase 1: a novel drug target in cancer development

Neville J Butcher1, Rodney F Minchin

  • 1School of Biomedical Sciences, University of Queensland, Brisbane, QLD 4072 Australia.

Pharmacological Reviews
|November 18, 2011
PubMed

Insights

Human arylamine N-acetyltransferase 1 (NAT1) plays a role in drug metabolism and carcinogen detoxification. Emerging research highlights NAT1

Area of Science:

  • Biochemistry
  • Pharmacology
  • Genetics

Background:

  • Human arylamine N-acetyltransferases (NAT1 and NAT2) are crucial for drug metabolism.
  • Genetic polymorphisms in NAT genes influence cancer risk by affecting carcinogen metabolism.
  • NAT1, unlike NAT2, exhibits broad tissue expression and is subject to post-translational and environmental regulation.

Purpose of the Study:

  • To explore the multifaceted roles of NAT1 beyond drug metabolism and carcinogen detoxification.
  • To investigate the emerging role of NAT1 in cancer cell growth, survival, and chemotherapy resistance.
  • To evaluate NAT1 as a potential therapeutic target for cancer treatment.

Main Methods:

  • Literature review of studies on NAT1 function, genetics, and cancer biology.
  • Analysis of gene expression data and enzymatic activity in various cancer types.
  • Examination of the relationship between NAT1 and cellular processes like folate homeostasis.

Main Results:

  • NAT1 is frequently overexpressed in multiple cancer types, correlating with increased cancer cell survival.
  • NAT1 overexpression contributes to chemotherapy resistance.
  • While a link to folate homeostasis is suggested, the precise mechanisms of NAT1's role in cancer cell growth require further elucidation.

Conclusions:

  • NAT1's role extends to promoting cancer cell growth and therapeutic resistance.
  • NAT1 represents a promising target for novel anti-cancer drug development.
  • Small molecule inhibitors targeting NAT1 are warranted for preclinical and clinical evaluation.

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