Cyclin-dependent kinase inhibitor seliciclib shows in vitro activity in diffuse large B-cell lymphomas.

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Cyclin-dependent kinase inhibitor seliciclib shows in vitro activity in diffuse

large B-cell lymphomas.

K Lacrima, A Rinaldi, S Vignati, V , MG Tibiletti, G Gaidano, CV Catapano,

and F Bertoni

Leuk Lymphoma, January 1, 2007; 48(1): 158-67.

Laboratory of Experimental Oncology, Oncology Institute of Southern Switzerland

(IOSI), Bellinzona, Switzerland.

Despite recent improvements in treatment, a significant fraction of patients

with diffuse large B-cell lymphoma (DLBCL) still fail therapy. Therefore, new

therapeutic modalities are needed to advance the cure rate. Seliciclib (CYC202,

R-roscovitine) is a purine analog developed as an inhibitor of CDK2/cyclin E

CDK7/cyclin H and CDK9/cyclin T. Seliciclib has been shown to be active in

B-cell neoplasms, such as mantle cell lymphoma, chronic lymphocytic leukemia and

in multiple myeloma in vitro. The aim of this study was to assess the in vitro

activity of seliciclib in DLBCL. The anti-proliferative activity of seliciclib

was tested in nine human DLBCL cell lines and six DLBCL primary cell cultures.

The effects of seliciclib on the cell cycle and on apoptosis, as well as on

transcription-related proteins were assessed. The cell viability of all DLBCL

cell lines and primary cells was reduced by seliciclib treatment. The IC50 for

the cell lines ranged from 13 - 36 microm. The effect of seliciclib was

independent of the genetic aberrations characterizing the cell lines. After

seliciclib exposure cells accumulated in G2/M or in G1 phase, with most of the

cells showing signs of apoptosis. Despite the clear cytotoxic effect and

induction of apoptosis, this study could not identify a unique mechanism of

action. The in vitro data suggest that seliciclib is an active agent in DLBCL.

Its efficacy is apparently independent of the underlying chromosomal

translocations characteristic of DLBCL. The drug might represent a new

therapeutic agent in this lymphoma sub-type.

PMID: 17325859