Journal Article

Induction of cyclin-dependent kinase inhibitors and G<sub>1</sub> prolongation by the chemopreventive agent <i>N</i>-acetylcysteine

Ming Liu, Norbert M. Wikonkal and Douglas E. Brash

in Carcinogenesis

Volume 20, issue 9, pages 1869-1872
Published in print September 1999 | ISSN: 0143-3334
Published online September 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.9.1869
Induction of cyclin-dependent kinase inhibitors and G1 prolongation by the chemopreventive agent N-acetylcysteine

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Cyclin-dependent kinase (cdk) inhibitors, such as p16INK4a and p21WAF1/CIP1, often inhibit G1 cyclin kinases and result in G1 arrest. It has been suggested that p21WAF1/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 (NAC), a well-known chemopreventive agent, induces p16INK4a and p21WAF1/CIP1 gene expression and prolongs cell-cycle transition through G1 phase. A portion of the G1 arrest by NAC is governed by p16INK4a; 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.

Keywords: BSO, buthionine sulfoximine; cdk, cyclin-dependent kinase; GSH, glutathione; NAC, N-acetylcysteine.

Journal Article.  2927 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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