Beta-Blockers and Berberine: A Possible Dual Approach to Contrast Neuroblastoma Growth and Progression

Abstract

The use of nutraceuticals during cancer treatment is a long-lasting debate. Berberine (BBR) is an isoquinoline quaternary alkaloid extracted from a variety of medicinal plants. BBR has been shown to have therapeutic effects in different pathologies, particularly in cancer, where it affects pathways involved in tumor progression. In neuroblastoma, the most common extracranial childhood solid tumor, BBR, reduces tumor growth by regulating both stemness and differentiation features and by inducing apoptosis. At the same time, the inhibition of β-adrenergic signaling leads to a reduction in growth and increase of differentiation of neuroblastoma. In this review, we summarize the possible beneficial effects of BBR in counteracting tumor growth and progression in various types of cancer and, in particular, in neuroblastoma. However, BBR administration, besides its numerous beneficial effects, presents a few side effects due to inhibition of MAO A enzyme in neuroblastoma cells. Therefore, herein, we proposed a novel therapeutic strategy to overcome side effects of BBR administration consisting of concomitant administration of BBR together with β-blockers in neuroblastoma.

Natural Products Inhibitors of Monoamine Oxidases—Potential New Drug Leads for Neuroprotection, Neurological Disorders, and Neuroblastoma

“…Berberine treatment produced the induction of neuronal cell differentiation, attenuated cancer stemness markers, and potentiated G0/G1 cell cycle arrest in neuro2a (N2a) neuroblastoma cells [216]. Concurrent inhibition of β-adrenergic signaling pathways with a β-blocker and inhibition of MAO-A with berberine 6 produced attenuation of tumor growth and an increase in differentiation of cells [217].…”

Berberine as a Potential Anticancer Agent: A Comprehensive Review

“…Around the same time, inhibiting the adrenergic signal slows neuroblastoma development and increases cell differentiation. Calvani et al [ 108 ] have summarized the potential benefits of BBR in inhibiting tumor growth and development in different types of cancer, especially neuroblastoma [ 108 ], BBR (6.25–200 μmol/L, 6–48 h) impaired cell viability and proliferation of U87 and U251 human glioblastoma cell lines in BALB/c nude mice (IC 50 of 42 and 32 μmol/L, respectively). BBR (50 μmol/L) prevented HUVEC cell migration in the transwell assay by 67.50 ± 8.14% and the Matrigel assay by 73.00 ± 1.12% [ 109 ].…”

Therapeutic Screening of Herbal Remedies for the Management of Diabetes

“…During DM there is a relationship between inflammation and oxidative stress which leads to the creation of proinflammatory cytokines such as IL-6 and TNF-α [104]. It was reported that BER counteracts some inflammatory processes where it attenuates NADPH oxidase (NOX) that is responsible for reactive oxygen species (ROS) generation, thereby decreasing AGEs and increasing endothelial function in DM [105]. BER displayed a tendency to ameliorate the inflammation resulting from DM via various pathways, e.g., suppression of phosphorylated Toll-like receptor (TLR) and IkB kinase-β (IKK-β) that is responsible for NF-κB activation; thus, BER interferes with the serine phosphorylation of IRS and diminishes insulin resistance [106].…”