title: Sulforaphane suppresses in vitro and in vivo lung tumorigenesis through downregulation of HDAC activity.
abstract: BACKGROUND
  Sulforaphane (SFN), an isothiocyanate isolated from broccoli, has been reported to have chemopreventive activity. However, the effects of SFN on lung cancer have not been investigated. In this study, we investigate the chemopreventive role of SFN through the inhibition of histone deacetylase (HDAC) in two different lung cancer cells by in vitro and in vivo mouse models.
  
  
  METHODS
  A549 and H1299 lung cancer cells were treated with SFN for 48h. The HDAC activity, expression of acetylated histones H3 and H4, apoptosis and cell cycles were analyzed by western blot, qRT-PCR and flow cytometry. A549 cells were implanted into the immunocompromised mice for xenografts.
  
  
  RESULTS
  The results showed that SFN inhibited HDAC activity and increased the levels of acetylated histones H3 and H4 in all two lung cancer cells. Further, SFN induced apoptosis, increased the accumulation of cells at G0/G1 and G2/M and arrest cells at S phase. We also found that a concomitant increase of apoptosis related proteins by SFN administration. More interestingly, SFN suppressed the lung cancer growth in xenograft mouse model.
  
  
  CONCLUSIONS
  In conclusion, the chemopreventive effect of SFN is associated with inhibition of HDAC activity, thereby attenuating lung cancer growth. Therefore, these findings suggest that SFN may be a therapeutic agent for lung cancer through the inhibition of HDAC.
authors.affiliation: Department of Medical Imaging, Linyi People's Hospital, Linyi, Shandong 276003, PR China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Jiang
authors.affiliation: Department of Medical Imaging, Linyi People's Hospital, Linyi, Shandong 276003, PR China.
authors.forename: Shi-Juan
authors.initials: SJ
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Lanling People's Hospital, Lanling, Shandong 277700, PR China.
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Lanling People's Hospital, Lanling, Shandong 277700, PR China.
authors.forename: Hai-Qing
authors.initials: HQ
authors.lastname: Chen
authors.affiliation: Department of Intensive Care Unit (ICU), Rizhao People's Hospital, Rizhao, Shandong 276826, PR China. Electronic address: weiliubio@yahoo.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013454:Sulfoxides; D023041:Xenograft Model Antitumor Assays
chemical_list: D006657:Histones; D017879:Isothiocyanates; D013454:Sulfoxides; D006655:Histone Deacetylases; C016766:sulforaphane
keywords: Chemoprevention; HDAC; Lung cancer; Mouse xenografts; Sulforaphane