PMID- 27805058
OWN - NLM
STAT- MEDLINE
DCOM- 20180522
LR  - 20211204
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Nov 2
TI  - Sulforaphane, a natural component of broccoli, inhibits vestibular schwannoma 
      growth in vitro and in vivo.
PG  - 36215
LID - 10.1038/srep36215 [doi]
LID - 36215
AB  - 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.
FAU - Kim, Bo Gyung
AU  - Kim BG
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University 
      College of Medicine, Bucheon, Korea.
FAU - Fujita, Takeshi
AU  - Fujita T
AD  - Department of Otolaryngology, Kindai University Faculty of Medicine, Osaka, 
      Japan.
AD  - Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and 
      Ear Infirmary, Boston, MA, USA.
AD  - Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA.
FAU - Stankovic, Konstantina M
AU  - Stankovic KM
AD  - Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and 
      Ear Infirmary, Boston, MA, USA.
AD  - Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA.
FAU - Welling, D Bradley
AU  - Welling DB
AD  - Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA.
FAU - Moon, In Seok
AU  - Moon IS
AD  - Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, 
      Korea.
FAU - Choi, Jae Young
AU  - Choi JY
AD  - Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, 
      Korea.
FAU - Yun, Jieun
AU  - Yun J
AD  - Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, 
      Cheongju, Korea.
FAU - Kang, Jong Soon
AU  - Kang JS
AD  - Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, 
      Cheongju, Korea.
FAU - Lee, Jong Dae
AU  - Lee JD
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Soonchunhyang University 
      College of Medicine, Bucheon, Korea.
AD  - Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and 
      Ear Infirmary, Boston, MA, USA.
AD  - Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20161102
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Isothiocyanates)
RN  - 0 (Sulfoxides)
RN  - GA49J4310U (sulforaphane)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Brassica/*chemistry
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Female
MH  - Humans
MH  - Isothiocyanates/*pharmacology
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neuroma, Acoustic/*drug therapy/pathology
MH  - Phytotherapy
MH  - Sulfoxides
MH  - *Xenograft Model Antitumor Assays
PMC - PMC5090244
EDAT- 2016/11/03 06:00
MHDA- 2018/05/23 06:00
PMCR- 2016/11/02
CRDT- 2016/11/03 06:00
PHST- 2016/06/17 00:00 [received]
PHST- 2016/10/12 00:00 [accepted]
PHST- 2016/11/03 06:00 [pubmed]
PHST- 2018/05/23 06:00 [medline]
PHST- 2016/11/03 06:00 [entrez]
PHST- 2016/11/02 00:00 [pmc-release]
AID - srep36215 [pii]
AID - 10.1038/srep36215 [doi]
PST - epublish
SO  - Sci Rep. 2016 Nov 2;6:36215. doi: 10.1038/srep36215.