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

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

Journal

Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298

Informations de publication

Date de publication:
15 07 2023
Historique:
received: 13 02 2023
revised: 04 05 2023
accepted: 30 05 2023
medline: 27 6 2023
pubmed: 18 6 2023
entrez: 17 6 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 37329676
pii: S0968-0896(23)00214-6
doi: 10.1016/j.bmc.2023.117366
pii:
doi:

Substances chimiques

mezerein 34807-41-5
Latex 0
huratoxin 33465-16-6
Diterpenes 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

117366

Informations de copyright

Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Elise Crossay (E)

UMR 152 PharmaDev, Université de Toulouse, IRD, UPS, France.

Valérie Jullian (V)

UMR 152 PharmaDev, Université de Toulouse, IRD, UPS, France.

Manon Trinel (M)

UMR 152 PharmaDev, Université de Toulouse, IRD, UPS, France.

David Sagnat (D)

IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France; Toulouse Organoids Platform, Institut de Recherche en Santé Digestive, INSERM, Toulouse, France.

Dimitri Hamel (D)

IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France; LAAS-CNRS, Université de Toulouse, CNRS, Toulouse, France.

Emie Groppi (E)

UMR 152 PharmaDev, Université de Toulouse, IRD, UPS, France.

Corinne Rolland (C)

IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France.

Jean-Luc Stigliani (JL)

UPR 8241 LCC, Université de Toulouse, CNRS, France.

Kember Mejia (K)

Instituto de Investigaciones de la Amazonia Peruana (IIAP), Iquitos, Peru.

Billy Joel Cabanillas (BJ)

Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 15102, Peru.

Laurent Alric (L)

Pole Digestif, Centre Hospitalier Universitaire, Toulouse, France.

Etienne Buscail (E)

IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France; Département de Chirurgie Digestive, Unité de Chirurgie Colorectale, Centre Hospitalier Universitaire, Toulouse, France.

Chaker El Kalamouni (C)

UMR PIMIT, Université de La Réunion, INSERM U1187, CNRS 9192, IRD 249, La Réunion, France.

Patrick Mavingui (P)

UMR PIMIT, Université de La Réunion, INSERM U1187, CNRS 9192, IRD 249, La Réunion, France.

Céline Deraison (C)

IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France.

Claire Racaud-Sultan (C)

IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, France. Electronic address: claire.racaud@inserm.fr.

Nicolas Fabre (N)

UMR 152 PharmaDev, Université de Toulouse, IRD, UPS, France. Electronic address: nicolas.fabre@univ-tlse3.fr.

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Classifications MeSH