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
  • 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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