This paper suggests that high levels of Berberine may be counterproductive.
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.
Belanova A1, Beseda D1, Chmykhalo V1, Stepanova A1, Belousova M2, Khrenkova V3, Gavalas N4, Zolotukhin P1.
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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 Berberine.
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KEYWORDS:
AP-1; Berberine; HIF1A; HeLa cells; NFE2L2; NFκB; mRNA; pre-mRNA; signaling pathways