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

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.

Ascorbic Acid and Glucosinolate Levels in New Czech Cabbage Cultivars: Effect of Production System and Fungal Infection

“…The occurrence of sulforaphane was, also, reported in broccoli, Brussels sprouts, cauliflower, and some cabbage cv. [ 48 ]. Albatros and Target cv.…”

“…are shown to be an important source of GSLs, and their degradation products enrich the human diet with the GSL-based, health-beneficial compounds. These molecules were implicated in protection against various types of cancer, high blood pressure reduction, heart disease prevention, and the control of blood glucose level to help in the type 2 diabetes [ 44 , 48 ].…”

Sulforaphane from Cruciferous Vegetables: Recent Advances to Improve Glioblastoma Treatment

“…In particular, there is a growing interest in identifying specific chemoprotective constituents in cruciferous vegetables and their mechanisms of action. The isothiocyanate (ITC, Figure 1 a) sulforaphane (SFN, Figure 1 b), which is converted from a major glucosinolate in broccoli/broccoli sprouts, has been shown to prevent chemically induced cancers in animal models and to inhibit the growth of established tumors [ 11 , 12 , 13 ].…”

A Unified Methodological Framework for Vestibular Schwannoma Research

“…VS and GAN cells in culture can be exposed to chemically active substances, such as nonsteroidal anti-inflammatory drugs, small interfering RNAs (siRNAs), or natural organic compounds to elucidate disease-specific molecular mechanisms or to test a therapeutic target 13,14,29 .…”