New cell proliferation blockers

Cellular senescence is a state of terminal arrest in which cells remain metabolically active for extended periods but can no longer respond to mitogenic stimulation. This can be exploited as a strategy to prevent tumorigenesis, but the molecular pathways involved in the induction of senescence remain unclear. In December 1 Journal of Clinical Investigation, Dimitri Lodygin and colleagues at the Max-Planck-Institute of Biochemistry, Munich, Germany, show that the drug LY83583 induces cellular senescence without inducing DNA damage (Journal of Clinical Investigation 110:1717-1727, December 1, 2002).

Lodygin et al. examined the effect of 6-anilino-5,8-quinolinequinone (LY83583 or LY), an inhibitor of guanylate cyclase in several human and murine cell types. They observed that in primary human diploid fibroblasts (HDFs) cell lines the treatment with LY induced cellular senescence via induction of the Cdk inhibitor p21WAF1/SDI/CIP1. The effect was dependent on p21 but not on p53, which suggests that LY does not induce ...