Epigenetic mechanism of growth inhibition induced by phenylhexyl isothiocyanate in prostate cancer cells.
BACKGROUND
Isothiocyanates, the constituents of cruciferous vegetables, may be able to prevent prostate cancer. The hypothesis that they could remodel chromatins and activate cell cycle inhibitors, such as p21 for growth inhibition, was tested.


METHODS
Prostate cancer LNCaP cells were exposed to phenylhexyl isothiocyanate (PHI). The status of histone acetylation and the activity of histone deacetylases (HDAC) were investigated. The association of p21 with hyperacetylated histones was examined by chromatin immunoprecipitation.


RESULTS
The PHI-exposed LNCaP cells had diminished activity of HDAC 1 and 2. Global and selective histone acetylation was enhanced, consistent with the signs of chromatin unfolding. The hyperacetylated histones increased accessibility to the p21 promoter for transcription, leading to G1 arrest and apoptosis.


CONCLUSIONS
PHI inhibited the activity of HDAC and remodeled chromatins to activate p21 for cell cycle arrest, underlying an epigenetic mechanism regulating the growth of prostate cancer cells.
Beklemisheva
Anastasia A
AA
Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.
Fang
Yuqiang
Y
Feng
Jingyang
J
Ma
Xudong
X
Dai
Wei
W
Chiao
Jen Wei
JW
D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D017879:Isothiocyanates; C073279:6-phenylhexyl isothiocyanate