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

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.

Berberine Inhibits Herpes Simplex Virus 1 Replication in HEK293T Cells

“…Cytotoxicity is a factor that must be considered in seeking a candidate for HSV-1 treatment. A study showed that berberine exerted an anticancer impact against HeLa cells with CC 50 of 12.08 μg/mL whereas 5 Computational and Mathematical Methods in Medicine exhibited low toxicity (CC 50 : 71.14 μg/mL) on Vero cells [31]. Chin et al found that the CC 50 of berberine extracted from Coptis chinensis on Vero cells was 392.5 μM, the IC 50 was 66.49 μM, and the SI was 5.9 [32].…”

Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review

“…Berberine inhibits the release of MMP-2 from tumor cells and thus inhibits tumor cell destruction of the tissue matrix. Berberine increased the activities of numerous proteins involved in proliferation, such as Janus Kinase 2 (JAK2), Phosphoinositide 3-kinase (PI3K), activator protein-1 (AP-1), and NF-kappaB (Mahata et al, 2011;Fu et al, 2013;Wu et al, 2013;Belanova et al, 2019;El-Zeftawy et al, 2019;Jiang et al, 2019). These proteins decreased IL-8 expression in the TNBC cell line, MDA-MB-231.…”

Recent Advances in Berberine Inspired Anticancer Approaches: From Drug Combination to Novel Formulation Technology and Derivatization

“…As with its anti-inflammatory effect, berberine can modulate the transcription factor nuclear factor-κB (NF-kB) that is linked to the expression of cytokines and other proinflammatory mediators associated with cell migration and cancer metastasis. Hence, inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as a result of NF-kB suppression is a key feature of angiogenesis inhibition by berberine [26,54]. Through suppression of COX and related signalling, those protein mediators critically involved in cancer metastasis such as matrix metalloproteinase (MMP) and vascular endothelial growth factor (VEGF) have been shown to be suppressed by berberine in various experimental models of cancer metastasis [27,29,35,45,49,54].…”