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

[ Vol. 19 , Issue. 4 ]

Author(s):

Anna Belanova, Darya Beseda, Victor Chmykhalo, Alisa Stepanova, Mariya Belousova, Vera Khrenkova, Nikolaos Gavalas and Peter Zolotukhin*   Pages 487 - 501 ( 15 )

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.

Affiliation:

Biomedical Innovations LLC, 112 Mechnikova st., 344013, Rostov-on-Don, Biomedical Innovations LLC, 112 Mechnikova st., 344013, Rostov-on-Don, Biomedical Innovations LLC, 112 Mechnikova st., 344013, Rostov-on-Don, Biomedical Innovations LLC, 112 Mechnikova st., 344013, Rostov-on-Don, English Language Department for Natural Sciences Faculties, Southern Federal University, 5 Sorge st., 344090, Rostov-on-Don, Rostov State Medical University, 119 Suvorova st., 344022, Rostov-on-Don, Division of Clinical Therapeutics, National and Kapodistrian University of Athens, 80 Vas. Sofias Av., 11521, Athens, Biomedical Innovations LLC, 112 Mechnikova st., 344013, Rostov-on-Don

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