Berberine Effects on NFκB, HIF1A and NFE2L2/AP-1 Pathways in HeLa Cells

Author(s): Anna Belanova, Darya Beseda, Victor Chmykhalo, Alisa Stepanova, Mariya Belousova, Vera Khrenkova, Nikolaos Gavalas, Peter Zolotukhin*.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 19 , Issue 4 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Berberine has multitudinous anti-cancer stem cells effects making it a highly promising candidate substance for the next-generation cancer therapy. However, berberine modes of action predispose it to significant side-effects that probably limit its clinical testing and application.

Materials and Methods: HeLa cells were treated with two concentrations of berberine (30 and 100 µM) for 24 hours to assess the functioning of the NFE2L2/AP-1, NFκB and HIF1A pathways using 22 RNAs expression qPCR-based analysis.

Results: Berberine effects appeared to be highly dose-dependent, with the lower concentration being capable of suppressing the NFκB functioning and the higher concentration causing severe signaling side-effects seen in the HIF1A pathway and the NFE2L2 sub-pathways, and especially and more importantly in the AP-1 sub-pathway.

Conclusion: The results of the study suggest that berberine has clinically valuable anti-NFκB effects however jeopardized by its side effects on the HIF1A and especially NFE2L2/AP-1 pathways, its therapeutic window phenomenon and its cancer type-specificity. These, however, may be ameliorated using the cocktail approach, provided there is enough data on signaling effects of berberine.

Keywords: Berberine, HeLa cells, NFκB, HIF1A, NFE2L2, AP-1, pre-mRNA, mRNA, signaling pathways.

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VOLUME: 19
ISSUE: 4
Year: 2019
Page: [487 - 501]
Pages: 15
DOI: 10.2174/1871520619666181211121405
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