Activités antitumorale et antimétastasique des alkylglycérols naturels : relation structure-activité

¹ Laboratoire de pharmacologie moléculaire, 2 avenue du Pr Léon Bernard, 35043 Rennes cedex
² École nationale supérieure de chimie de Rennes, avenue du Général Leclerc, CS 50837 Rennes cedex 7, et université européenne de Bretagne

^* alain.legrand@univ-rennes1.fr

Abstract

Oral alkylglycerols (AKG) from shark liver oil (SLO) have multiple biological activities including immuno-stimulation and anti-tumour properties. In several cell types they are incorporated into phospholipids and therefore they may produce modified messengers and mediators following cellular activation of the phospholipase pathway. Structure of naturally occurring AKG vary depending on length and unsaturation of the alkyl chain. We synthesized six of the major natural constituants of AKG from SLO and tested their anti-tumour and anti-metastasis activities on a model of solid tumour grafted in mice. We found that unsaturated compounds were the most active for reducing tumour volume, lung metastasis number, and splenomegaly. Saturated compounds had weaker, no, or deleterious activities on this model. These data suggest that the selective use of unsaturated natural AKG would improve anti-tumour activities as compared to natural mix of AKG.