Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine

Ming Liu, N. Wikonkál, Douglas E. Brash

Research output: Contribution to journalArticle

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Abstract

Cyclin-dependent kinase (cdk) inhibitors, such as p16(INK4a) and p21(WAF1/CIP1), often inhibit G1 cyclin kinases and result in G1 arrest. It has been suggested that p21(WAF1/CIP1) may also play a role in other chemopreventive activities such as DNA repair, slowdown of DNA replication and induction of cellular differentiation. In this report we demonstrate that the antioxidant N-acetylcysteine (NAG), a well-known chemopreventive agent, induces p16(INK4a) and p21(WAF1/CIP1) gene expression and prolongs cell-cycle transition through G1 phase. A portion of the G1 arrest by NAC is governed by p16(INK4a); it is independent of p53. NAC's usual mechanism of increasing intracellular glutathione level is not required for the G1 arrest. An antioxidant whose action is limited to scavenging radicals, Trolox, does not induce G1 arrest. Taken together, these results suggest a potential novel molecular basis for chemoprevention by NAC.

Original languageEnglish
Pages (from-to)1869-1872
Number of pages4
JournalCarcinogenesis
Volume20
Issue number9
DOIs
Publication statusPublished - 1999

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Cyclin-Dependent Kinases
Acetylcysteine
Antioxidants
Cyclin G1
Chemoprevention
G1 Phase
DNA Replication
DNA Repair
Glutathione
Cell Cycle
Phosphotransferases
Gene Expression
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid

ASJC Scopus subject areas

  • Cancer Research

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Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine. / Liu, Ming; Wikonkál, N.; Brash, Douglas E.

In: Carcinogenesis, Vol. 20, No. 9, 1999, p. 1869-1872.

Research output: Contribution to journalArticle

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