Cyclin-dependent kinase 5 mediates pleiotrophin-induced endothelial cell migration.

Pleiotrophin (PTN) stimulates endothelial cell migration through binding to receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and αβ integrin. Screening for proteins that interact with RPTPβ/ζ and potentially regulate PTN signaling, through mass spectrometry analysis, identified cyclin-dependent kinase 5 (CDK5) activator p35 among the proteins displaying high sequence coverage. Interaction of p35 with the serine/threonine kinase CDK5 leads to CDK5 activation, known to be implicated in cell migration.

DNA fragmentation induced by all-trans retinoic acid and its steroidal analogue EA-4 in C2 C12 mouse and HL-60 human leukemic cells in vitro.

We have recently shown that retinoic acid induces micronucleation mainly via chromosome breakage (Alakhras et al. Cancer Lett 2011; 306: 15-26). To further study retinoic acid clastogenicity and evaluate DNA damaging potential we investigated the ability of (a) all-trans retinoic acid and its steroidal analogue EA-4 to induce DNA fragmentation by using Comet assay under alkaline unwinding and neutral condition electrophoresis, and (b) the retinoids under study to induce small (0-1 kb) DNA fragments.

Pyrrolo[2,3-α]carbazole derivatives as topoisomerase I inhibitors that affect viability of glioma and endothelial cells in vitro and angiogenesis in vivo.

Topoisomerase I is one of the most significant molecular targets through which indolocarbazoles inhibit tumour growth. In the present work, we studied the effect of new pyrrolo[2,3-α]carbazole derivatives on topoisomerase I activity in vitro, as well as on the viability of glioma and endothelial cells in vitro and on angiogenesis in vivo. All the tested compounds significantly decreased topoisomerase I activity in a concentration dependent manner, with the most effective being 1c, 1d(1), 1d(2) and 1f.