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Anticancer Agents Med Chem. 2018 Dec 11. doi: 10.2174/1871520619666181211121405. [Epub ahead of print]

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

Author information

1
Biomedical Innovations LLC, 112 Mechnikova st., 344013, Rostov-on-Don. Russian Federation.
2
English language department for natural sciences faculties, Southern federal university, 5 Sorge st., 344090, Rostov-on-Don. Russian Federation.
3
Rostov state medical university, 119 Suvorova st., 344022, Rostov-on-Don. Russian Federation.
4
Division of Clinical Therapeutics, National and Kapodistrian University of Athens, 80 Vas. Sofias Av., 11521, Athens. Russian Federation.

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 METHOD:

HeLa cells were treated with two concentrations of berberine (30 and 100 μM) for 24 hours to asses 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 barbering.

KEYWORDS:

AP-1; Berberine; HIF1A; HeLa cells; NFE2L2; NFκB; mRNA; pre-mRNA; signaling pathways

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