Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (26)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Liu, M.
Right arrow Articles by Brash, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, M.
Right arrow Articles by Brash, D. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Carcinogenesis, Vol. 20, No. 9, 1869-1872, September 1999
© 1999 Oxford University Press

Short Communications

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

Ming Liu1, Norbert M. Wikonkal1 and Douglas E. Brash1,2,3

1 Department of Therapeutic Radiology and
2 Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8040, USA

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.

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

3 To whom correspondence should be addressed Email: douglas.brash{at}yale.edu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
A. A. Goyeneche, R. W. Caron, and C. M. Telleria
Mifepristone Inhibits Ovarian Cancer Cell Growth In vitro and In vivo
Clin. Cancer Res., June 1, 2007; 13(11): 3370 - 3379.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. H. Sarsour, M. Agarwal, T. K. Pandita, L. W. Oberley, and P. C. Goswami
Manganese Superoxide Dismutase Protects the Proliferative Capacity of Confluent Normal Human Fibroblasts
J. Biol. Chem., May 6, 2005; 280(18): 18033 - 18041.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
D. N. Seril, J. Liao, K.-L. K. Ho, C. S. Yang, and G.-Y. Yang
Inhibition of chronic ulcerative colitis-associated colorectal adenocarcinoma development in a murine model by N-acetylcysteine
Carcinogenesis, June 1, 2002; 23(6): 993 - 1001.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
H. Witschi, I. Espiritu, M. Suffia, and K. E. Pinkerton
Expression of cyclin D1/2 in the lungs of strain A/J mice fed chemopreventive agents
Carcinogenesis, February 1, 2002; 23(2): 289 - 294.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Albini, M. Morini, F. D'Agostini, N. Ferrari, F. Campelli, G. Arena, D. M. Noonan, C. Pesce, and S. De Flora
Inhibition of Angiogenesis-driven Kaposi's Sarcoma Tumor Growth in Nude Mice by Oral N-Acetylcysteine
Cancer Res., November 1, 2001; 61(22): 8171 - 8178.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. De Flora, A. Izzotti, F. D'Agostini, and R. M. Balansky
Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points
Carcinogenesis, July 1, 2001; 22(7): 999 - 1013.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. A. Stivala, M. Savio, F. Carafoli, P. Perucca, L. Bianchi, G. Maga, L. Forti, U. M. Pagnoni, A. Albini, E. Prosperi, et al.
Specific Structural Determinants Are Responsible for the Antioxidant Activity and the Cell Cycle Effects of Resveratrol
J. Biol. Chem., June 15, 2001; 276(25): 22586 - 22594.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.