Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect.

Abstract : Erythroleukemia is generally associated with a very poor response and survival to current available therapeutic agents. Cyclooxygenase-2 (COX-2) has been described to play a crucial role in the proliferation and differentiation of leukemia cells, this enzyme seems to play an important role in chemoresistance in different cancer types. Previously, we demonstrated that diosgenin, a plant steroid, induced apoptosis in HEL cells with concomitant COX-2 overexpression. In this study, we investigated the antiproliferative and apoptotic effects of cyclopamine and jervine, two steroidal alkaloids with similar structures, on HEL and TF1a human erythroleukemia cell lines and, for the first time, their effect on COX-2 expression. Cyclopamine, but not jervine, inhibited cell proliferation and induced apoptosis in these cells. Both compounds induced COX-2 overexpression which was responsible for apoptosis resistance. In jervine-treated cells, COX-2 overexpression was NF-κB dependent. Inhibition of NF-κB reduced COX-2 overexpression and induced apoptosis. In addition, cyclopamine induced apoptosis and COX-2 overexpression via PKC activation. Inhibition of the PKC pathway reduced both apoptosis and COX-2 overexpression in both cell lines. Furthermore, we demonstrated that the p38/COX-2 pathway was involved in resistance to cyclopamine-induced apoptosis since p38 inhibition reduced COX-2 overexpression and increased apoptosis in both cell lines.
Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal-unilim.archives-ouvertes.fr/hal-00937762
Contributeur : Vincent Sol <>
Soumis le : mardi 28 janvier 2014 - 17:58:30
Dernière modification le : mardi 20 mars 2018 - 16:36:39

Identifiants

Collections

Citation

Lamia Ghezali, David Yannick Leger, Youness Limami, Jeanne Cook-Moreau, Jean-Louis Beneytout, et al.. Cyclopamine and jervine induce COX-2 overexpression in human erythroleukemia cells but only cyclopamine has a pro-apoptotic effect.. Experimental Cell Research, Elsevier, 2013, 319 (7), pp.1043-53. ⟨10.1016/j.yexcr.2013.01.014⟩. ⟨hal-00937762⟩

Partager

Métriques

Consultations de la notice

171