Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo.

Bo Gyung Kim,Jong Soon Kang,Jong Dae Lee,Jae Young Choi,Takeshi Fujita,D Bradley Welling,Jieun Yun,Konstantina M Stankovic,In Seok Moon

doi:10.1038/srep36215

Abstract

Vestibular schwannoma (VS) is an intracranial tumor that causes significant morbidity, including hearing loss, tinnitus, dizziness, and possibly even death from brainstem compression. However, FDA-approved pharmacologic treatments for VS do not exist. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli, with potent chemoprotective effects in several cell types. Our objective was to determine whether SFN is effective against VS in vitro and in vivo. Human primary VS cells, HEI-193 schwannoma cells, and SC4 Nf2−/− Schwann cells were used to investigate the inhibitory effects of SFN in vitro. Cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, and cell viability and metabolic activity was calculated by MTT assay. Apoptosis was measured by flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and Western blot for cleaved caspases. A mouse model with a murine schwannoma allograft was also used to examine the antitumor activity of SFN. SFN exhibited significant antiproliferative activity in schwannoma cells in vitro, via the inhibition of HDAC activity and the activation of ERK. SFN treatment induced apoptosis and cell cycle arrest at the G2/M phase. SFN also significantly inhibited schwannoma growth in vivo. Our preclinical studies motivate a future prospective clinical study of SFN for the treatment of VS.

Highlights

Several of these agents are capable of preventing but even treating some cancers[5]
Sulforaphane inhibits the proliferation of primary human vestibular schwannoma cells and an neurofibromatosis type 2 (NF2)-derived cell line in vitro
Because sulforphane is a potent inhibitor of histone deacetylase (HDAC) in several malignancies[7], we studied whether it had a similar effect on non-malignant schwannoma cells

Summary

Introduction

Several of these agents are capable of preventing but even treating some cancers[5]. A dietary agent extracted from cruciferous vegetables, and its potential to inhibit VS growth. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables, such as broccoli. SFN has been shown to exhibit chemoprotective effects for various tumors, including those of the prostate, lung, breast and colon, in vitro and in vivo[6,7,8]. These studies have shown that SFN significantly affects cell survival and leads to apoptosis through a variety of molecular mechanisms, including the potent inhibition of histone deacetylase (HDAC)[9,10,11]. As there have been no reports examining the effect of SFN on vestibular schwannoma, here we characterize the ilnhibitory effects of SFN on VS cells in vitro using primary human VS cells and VS-derived cell lines, and in vivo using a mouse model with a murine schwannoma allograft

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Conclusion