2. Academic Validation
  3. Daphnanes diterpenes from the latex of Hura crepitans L. and their PKCζ-dependent anti-proliferative activity on colorectal cancer cells

Daphnanes diterpenes from the latex of Hura crepitans L. and their PKCζ-dependent anti-proliferative activity on colorectal cancer cells

  • Bioorg Med Chem. 2023 Jul 15:90:117366. doi: 10.1016/j.bmc.2023.117366.
Elise Crossay 1,  Valérie Jullian 1,  Manon Trinel 1,  David Sagnat 2,  Dimitri Hamel 3,  Emie Groppi 1,  Corinne Rolland 4,  Jean-Luc Stigliani 5,  Kember Mejia 6,  Billy Joel Cabanillas 7,  Laurent Alric 8,  Etienne Buscail 9,  Chaker El Kalamouni 10,  Patrick Mavingui 10,  Céline Deraison 4,  Claire Racaud-Sultan 11,  Nicolas Fabre 12
Affiliations

Affiliations

  • 1 UMR 152 PharmaDev, Université de Toulouse, IRD, UPS, France.
  • 2 IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France; Toulouse Organoids Platform, Institut de Recherche en Santé Digestive, INSERM, Toulouse, France.
  • 3 IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France; LAAS-CNRS, Université de Toulouse, CNRS, Toulouse, France.
  • 4 IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France.
  • 5 UPR 8241 LCC, Université de Toulouse, CNRS, France.
  • 6 Instituto de Investigaciones de la Amazonia Peruana (IIAP), Iquitos, Peru.
  • 7 Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 15102, Peru.
  • 8 Pole Digestif, Centre Hospitalier Universitaire, Toulouse, France.
  • 9 IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France; Département de Chirurgie Digestive, Unité de Chirurgie Colorectale, Centre Hospitalier Universitaire, Toulouse, France.
  • 10 UMR PIMIT, Université de La Réunion, INSERM U1187, CNRS 9192, IRD 249, La Réunion, France.
  • 11 IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France. Electronic address: [email protected].
  • 12 UMR 152 PharmaDev, Université de Toulouse, IRD, UPS, France. Electronic address: [email protected].
PMID: 37329676 DOI: 10.1016/j.bmc.2023.117366
Abstract

Hura crepitans L. (Euphorbiaceae) is a thorn-covered tree widespread in South America, Africa and Asia which produces an irritating milky latex containing numerous secondary metabolites, notably daphnane-type diterpenes known as Protein Kinase C activators. Fractionation of a dichloromethane extract of the latex led to the isolation of five new daphnane diterpenes (1-5), along with two known analogs (6-7) including huratoxin. Huratoxin (6) and 4',5'-epoxyhuratoxin (4) were found to exhibit significant and selective cell growth inhibition against colorectal Cancer cell line Caco-2 and primary colorectal Cancer cells cultured as colonoids. The underlying mechanism of 4 and 6 was further investigated revealing the involvement of PKCζ in the cytostatic activity.

Keywords

Caco-2 cells; Colorectal cancer; Daphnane diterpenes; Euphorbiaceae; Hura crepitans; Protein Kinase C.

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