Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

Autor: Vincent Sol, Mona Diab-Assaf, Antoine M. Saab, Fadi Esseily, Frederique Martin, Saada Diab, Lamia Ghezali, David Yannick Leger, Rania Azar, Chloe Fidanzi, Bertrand Liagre, Marion Millot
Přispěvatelé: Laboratoire de Chimie des Substances Naturelles (LCSN), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Biochemistry Department, Faculty of Science - Section II, Lebanese UniversityJdeidet, Lebanon, Laboratory science department Faculty of Puiblic Heath, lebanese University Jdeidet el Metn, Faculty of Sciences [Lebanese University], Lebanese University [Beirut] (LU)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: International Journal of Oncology
International Journal of Oncology, Spandidos Publications, 2015, 47 (1), pp.220-230. ⟨10.3892/ijo.2015.3012⟩
ISSN: 1019-6439
1791-2423
DOI: 10.3892/ijo.2015.3012⟩
Popis: International audience; The aim of this study was to describe and understand the relationship between cyclooxygenase-2 (COX-2) expression and apoptosis rate in erythroleukemia cells after apoptosis induction by Berberis libanotica (Bl) extract. To achieve this goal we used erythroleukemia cell lines expressing COX‑2 (HEL cell line) or not (K562 cell line). Moreover, we made use of COX‑2 cDNA to overexpress COX‑2 in K562 cells. In light of the reported chemopreventive and chemosensitive effects of natural products on various tumor cells and animal models, we postulated that our Bl extract may mediate their effects through apoptosis induction with suppression of cell survival pathways. Our study is the first report on the specific examination of intrinsic apoptosis and Akt/NF-κB/COX‑2 pathways in human erythroleukemia cells upon Bl extract exposure. Even if Bl extract induced apoptosis of three human erythroleukemia cell lines, a dominant effect of Bl extract treatment on K562 cells was observed resulting in activation of the late markers of apoptosis with caspase-3 activation, PARP cleavage and DNA fragmentation. Whereas, we showed that Bl extract reduced significantly expression of COX‑2 by a dose-dependent manner in HEL and K562 (COX‑2+) cells. Furthermore, in regard to our results, it is clear that the simultaneous inhibition of Akt and NF-κB signalling can significantly contribute to the anticancer effects of Bl extract in human erythroleukemia cells. We observed that the Bl extract is clearly more active than the berberine alone on the induction of DNA fragmentation in human erythro-leukemia cells.
Databáze: OpenAIRE