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

Diab,Saada; Fidanzi,Chloe; Léger,David  Y.; Ghezali,Lamia; Millot,Marion; Martin,Frédérique; Azar,Rania; Esseily,Fadi; Saab,Antoine; Sol,Vincent; Diab-Assaf,Mona; Liagre,Bertrand

doi:10.3892/ijo.2015.3012

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

Authors:
- Saada Diab
- Chloe Fidanzi
- David Y. Léger
- Lamia Ghezali
- Marion Millot
- Frédérique Martin
- Rania Azar
- Fadi Esseily
- Antoine Saab
- Vincent Sol
- Mona Diab-Assaf
- Bertrand Liagre
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Affiliations: Laboratory of Chemistry of Natural Substances, Faculty of Pharmacy, University of Limoges, FR 3503 GEIST, EA1069, Limoges, France, Molecular Tumorigenesis and Anticancer Pharmacology, EDST, Lebanese University, Hadath, Lebanon, Laboratory Science Department, Faculty of Public Health, Lebanese University, Jdeidet El Metn, Lebanon, Faculty of Sciences II, Chemistry Department, Lebanese University, Beirut, Lebanon
Published online on: May 18, 2015 https://doi.org/10.3892/ijo.2015.3012
Pages: 220-230

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Abstract

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.

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