Daphnanes diterpenes from the latex of Hura crepitans L. and activity against human colorectal cancer cells Caco-2

Manon Trinel (1) , Anne-Cécile Le Lamer (1) , Valérie Jullian (1, 2) , Denis Jacquemin (3) , Jérôme Graton (3) , Valérie Cristofoli (1) , Elise Crossay (1) , May Yassine (4) , Corinne Rolland (4) , Nathalie Vergnolle (4) , Kember Mejia (5) , Billy Joel Cabanillas (2) , Claire Racaud-Sultan (4) , Nicolas Fabre (1)

1 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
2 UPCH - Universidad Peruana Cayetano Heredia
3 CEISAM - Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation
4 IRSD - Institut de Recherche en Santé Digestive
5 IIAP - Instituto de Investigaciones de la Amazonía Peruana

Hura crepitans (Euphorbiaceae) is a tree from South America that produces an irritant latex used as a fish poison. A bio-guided fractionation of an ethanolic extract of the latex led to the isolation and structural identification of three known daphnane-type diterpenes (1-3) including huratoxin (1), together with two new analogues (4, 5). Compound 1 was found to exhibit significant and selective cell growth inhibition against the colorectal cancer cell line Caco-2, with morphological modifications suggesting formations mimicking the intestinal crypt architecture. The underlying mechanism of 1 was further investigated, in comparison with 12-O-tetradecanoylphorbol-13-acetate (TPA), revealing two different mechanisms.

Mots clés: Hura crepitans; daphnanes diterpenes; colorectal cancer; cytotoxicity; epithelial morphogenesis

Domaines: Botanique; Médecine humaine et pathologie; Cancer

Manon Trinel, Anne-Cécile Le Lamer, Valérie Jullian, Denis Jacquemin, Jérôme Graton, et al.. Daphnanes diterpenes from the latex of Hura crepitans L. and activity against human colorectal cancer cells Caco-2. Bioorganic Chemistry, 2020, 103, pp.1-13. ⟨10.1016/j.bioorg.2020.104132⟩. ⟨hal-03034627⟩