Skip Navigation


Annals of Oncology Advance Access originally published online on April 25, 2005
Annals of Oncology 2005 16(7):1169-1176; doi:10.1093/annonc/mdi217
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
16/7/1169    most recent
mdi217v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
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 (22)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Lacrima, K.
Right arrow Articles by Bertoni, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lacrima, K.
Right arrow Articles by Bertoni, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2005 European Society for Medical Oncology

In vitro activity of cyclin-dependent kinase inhibitor CYC202 (Seliciclib, R-roscovitine) in mantle cell lymphomas{dagger}

K. Lacrima1, A. Valentini1, C. Lambertini1, M. Taborelli1, A. Rinaldi1, E. Zucca2, C. Catapano1, F. Cavalli1,2, A. Gianella-Borradori3, D. E. MacCallum3 and F. Bertoni1,4,*

1 Experimental Oncology and 2 Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; 3 Cyclacel Ltd, Dundee, Scotland, UK; 4 Experimental Haematology, St Bartholomew's Hospital and The London Hospital, London, UK

*Correspondence to:Dr F. Bertoni, Experimental Oncology, Oncology Institute of Southern Switzerland, via Vincenzo Vela 6, 6500 Bellinzona, Switzerland. Tel: +41 (0)91 8200 367; Fax: +41 (0)91 8200 397; Email: frbertoni{at}mac.com

Background:: Mantle cell lymphoma (MCL) has the worst prognosis of all B-cell lymphomas and has poor response to conventional therapy. It is characterized by the presence of a chromosomal translocation t(11:14) (q13;q32) which results in deregulated cyclin D1 expression. Since defects in cell cycle regulation and apoptosis are primary events in MCL, small-molecule inhibitors of cdks–cyclins may play an important role in the therapy of this disorder. CYC202 (Seliciclib, R-roscovitine; Cyclacel Ltd., Dundee, UK) is a purine analogue and a selective inhibitor of the cdk2–cyclin E as well as cdk7–cyclin H and cdk9–cyclin T.

Materials and methods:: The activity of CYC202 was tested in four human MCL cell lines: REC, Granta-519, JeKo-1 and NCEB-1. The effect of CYC202 on the cell cycle and on apoptosis-, cell-cycle- and transcription-regulation-related proteins was assessed.

Results:: The IC50 was 25 µM for REC, Granta-519 and JeKo-1 cells and 50 µM for NCEB-1 cells. CYC202 caused an accumulation of cells in the G2–M phase of the cell cycle and apoptosis. CYC202 caused down-regulation of cyclin D1 and Mcl-1 protein levels, possibly because of the inhibition of transcription elongation.

Conclusions:: Our data suggest that CYC202 is an active agent in MCL. The concomitant decrease of the phosphorylated and total forms of RNA polymerase II suggests that this could be the main mechanism mediating the biological effects of CYC202 in MCL cells. The drug might represent a new therapeutic agent in this lymphoma subtype.

Key words: apoptosis, cdk inhibitor, cyclin D1, lymphoma


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
 BloodHome page
E. Ortega-Paino, J. Fransson, S. Ek, and C. A. K. Borrebaeck
Functionally associated targets in mantle cell lymphoma as defined by DNA microarrays and RNA interference
Blood, February 1, 2008; 111(3): 1617 - 1624.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
D. J. Kerr
KISS: the 2006 Annals of Oncology prizes
Ann. Onc., September 1, 2006; 17(9): 1341 - 1342.
[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.