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. MATERIALS AND 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. CONCLUSION: 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.
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. MATERIALS AND 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. CONCLUSION: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.
Authors: Sarandeep S S Boyanapalli; Wenji Li; Francisco Fuentes; Yue Guo; Christina N Ramirez; Ximena-Parades Gonzalez; Douglas Pung; Ah-Ng Tony Kong Journal: Pharmacol Res Date: 2016-11-03 Impact factor: 7.658
Authors: Eunah Kim; William H Bisson; Christiane V Löhr; David E Williams; Emily Ho; Roderick H Dashwood; Praveen Rajendran Journal: Curr Top Med Chem Date: 2016 Impact factor: 3.295