Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma growth in vitro and in vivo.
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.
Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon, Korea.
Bo Gyung
BG
Kim
Department of Otolaryngology, Kindai University Faculty of Medicine, Osaka, Japan.|Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.|Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA.
Takeshi
T
Fujita
Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.|Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA.
Konstantina M
KM
Stankovic
Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA.
D Bradley
DB
Welling
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
In Seok
IS
Moon
Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
Jae Young
JY
Choi
Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea.
Jieun
J
Yun
Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea.
Jong Soon
JS
Kang
Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University College of Medicine, Bucheon, Korea.|Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.|Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA.
Jong Dae
JD
Lee
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001937:Brassica / Q000737:chemistry*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009464:Neuroma, Acoustic / Q000188:drug therapy* / Q000473:pathology; D008517:Phytotherapy; D013454:Sulfoxides; D023041:Xenograft Model Antitumor Assays
D017879:Isothiocyanates; D013454:Sulfoxides; C016766:sulforaphane