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

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

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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.

Original languageEnglish
Article number36215
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Nov 2

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Acoustic Neuroma
Brassica
Neurilemmoma
Growth
Apoptosis
DNA Nucleotidylexotransferase
Tinnitus
In Vitro Techniques
sulforafan
G2 Phase
Schwann Cells
Dizziness
Bromodeoxyuridine
Caspases
Cell Cycle Checkpoints
Hearing Loss
Vegetables
Cell Division
Brain Stem
Allografts

All Science Journal Classification (ASJC) codes

  • General

Cite this

Kim, Bo Gyung ; Fujita, Takeshi ; Stankovic, Konstantina M. ; Welling, D. Bradley ; Moon, InSeok ; Choi, Jae Young ; Yun, Jieun ; Kang, Jong Soon ; Lee, Jong Dae. / Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo. In: Scientific reports. 2016 ; Vol. 6.
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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.",
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Kim, BG, Fujita, T, Stankovic, KM, Welling, DB, Moon, I, Choi, JY, Yun, J, Kang, JS & Lee, JD 2016, 'Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo', Scientific reports, vol. 6, 36215. https://doi.org/10.1038/srep36215

Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo. / Kim, Bo Gyung; Fujita, Takeshi; Stankovic, Konstantina M.; Welling, D. Bradley; Moon, InSeok; Choi, Jae Young; Yun, Jieun; Kang, Jong Soon; Lee, Jong Dae.

In: Scientific reports, Vol. 6, 36215, 02.11.2016.

Research output: Contribution to journalArticle

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AU - Kim, Bo Gyung

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AU - Welling, D. Bradley

AU - Moon, InSeok

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AU - Lee, Jong Dae

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