Anticancer alkaloid lamellarins inhibit protein kinases.

Dianne Baunbaek , Nolwenn Trinkler , Yoan Ferandin (1) , Olivier Lozach (1) , Poonsakdi Ploypradith , Somsak Rucirawat , Fumito Ishibashi , Masatomo Iwao , Laurent Meijer (1)

1 MCT - Molécules et cibles thérapeutiques

Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dual-specificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors.

Domaines: Biologie cellulaire

Dianne Baunbaek, Nolwenn Trinkler, Yoan Ferandin, Olivier Lozach, Poonsakdi Ploypradith, et al.. Anticancer alkaloid lamellarins inhibit protein kinases.. Marine drugs, 2008, 6 (4), pp.514-27. ⟨10.3390/md20080026⟩. ⟨hal-00416040⟩