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Biomed Pharmacother ; 78: 74-80, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26898427

RESUMO

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. CONCLUSION: 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.


Assuntos
Carcinogênese/patologia , Regulação para Baixo/efeitos dos fármacos , Histona Desacetilases/metabolismo , Isotiocianatos/farmacologia , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Acetilação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Camundongos Endogâmicos NOD , Camundongos SCID , Sulfóxidos , Ensaios Antitumorais Modelo de Xenoenxerto
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