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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

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 and Peter Zolotukhin*

Volume 19, Issue 4, 2019

Page: [487 - 501] Pages: 15

DOI: 10.2174/1871520619666181211121405

Price: $65

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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