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

Abstract

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.

Tea in Health and Disease

“…Farabegoli et al, discovered that the combinational treatment of EGCG and a rexinoid, 6-OH-11-O-hydroxyphenanthrene [IIF] inhibits neuroblastoma cell growth and neurosphere formation in vitro [8]; the authors concluded that the association of EGCG to IIF might be able to overcome the incomplete success of retinoid treatments in neuroblastoma patient without toxic effects.…”

MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products

“…EGCG is a biological polyphenol commonly detected in green tea [ 525 ]. Numerous studies have investigated the anti-cancer potential of EGCG and its benefits, such as reversal of drug resistance and inhibition of cancer stem cells [ 525 ]. Proteomics analysis demonstrated that the DEAD-box RNA helicase, p68, is a binding target of EGCG [ 526 ].…”

Cancer stem cells in neuroblastoma therapy resistance

“…Farabegoli et al [191] Drugs (combinations) tested, targeted molecular drivers and the studies are listed. A complete list if CSC-targeting compounds, mode of action in and beyond NB is discussed in detail elsewhere [188] specific candidate in all NB-CSCs within the tumor and (2) the presence of candidate marker(s) in normal non-tumorigenic stem cells highly limit their use in developing a CSC-targeted approach.…”