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Open AccessArticle

Epigallocatechin-3-gallate and 6-OH-11-O-Hydroxyphenanthrene Limit BE(2)-C Neuroblastoma Cell Growth and Neurosphere Formation In Vitro

1
Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, 40126 Bologna, Italy
2
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40138 Bologna, Italy
3
Department Biological, Geological, and Environmental Sciences (BiGeA), University of Bologna, 40126 Bologna, Italy
*
Author to whom correspondence should be addressed.
Nutrients 2018, 10(9), 1141; https://doi.org/10.3390/nu10091141
Received: 9 July 2018 / Revised: 9 August 2018 / Accepted: 20 August 2018 / Published: 22 August 2018
(This article belongs to the Special Issue Tea in Health and Disease)
We conducted an in vitro study combining a rexinoid, 6-OH-11-O-hydroxyphenanthrene (IIF), and epigallocatechin-3-gallate (EGCG), which is the main catechin of green tea, on BE(2)-C, a neuroblastoma cell line representative of the high-risk group of patients. Neuroblastoma is the most common malignancy of childhood: high-risk patients, having N-MYC over-expression, undergo aggressive therapy and show high mortality or an increased risk of secondary malignancies. Retinoids are used in neuroblastoma therapy with incomplete success: the association of a second molecule might improve the efficacy. BE(2)-C cells were treated by EGCG and IIF, individually or in combination: cell viability, as evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, was reduced, EGCG+IIF being the most effective treatment. Apoptosis occurred and the EGCG+IIF treatment decreased N-MYC protein expression and molecular markers of invasion (MMP-2, MMP-9 and COX-2). Zymography demonstrated nearly 50% inhibition of MMP activity. When BE(2)-C cells were grown in non-adherent conditions to enrich the tumor-initiating cell population, BE(2)-C-spheres were obtained. After 48 h and 72 h treatment, EGCG+IIF limited BE(2)-C-sphere formation and elicited cell death with a reduction of N-MYC expression. We concluded that the association of EGCG to IIF might be applied without toxic effects to overcome the incomplete success of retinoid treatments in neuroblastoma patients. View Full-Text
Keywords: EGCG; 6-OH-11-O-hydroxyphenanthrene; neuroblastoma; BE(2)-C; N-MYC; neuro-sphere EGCG; 6-OH-11-O-hydroxyphenanthrene; neuroblastoma; BE(2)-C; N-MYC; neuro-sphere
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MDPI and ACS Style

Farabegoli, F.; Govoni, M.; Spisni, E.; Papi, A. Epigallocatechin-3-gallate and 6-OH-11-O-Hydroxyphenanthrene Limit BE(2)-C Neuroblastoma Cell Growth and Neurosphere Formation In Vitro. Nutrients 2018, 10, 1141.

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