Study On Molecular Mechanisms Of Apoptosis Induced By Phenyhexyle Isothiocyanate (PHI) In Prostate Cancer PC3 Cell Line

Ojects To investigate PHI(phenyhexyle isothiocyanate) effect on cell apoptosis,histone acetylation and histone methylation,and Akt signaling pathway in prostate cancer cell line(PC3) in vitro.We further study its potential mechanism.Methods The viability of PC3 cells after treated with PHI was checked by MTT method.Apoptotic cells were measured by TUNNEL assay.The proteins of bcL-2,caspase-9,caspase-3,McL-1,Cyt-C,XIAP,histone acetylated H3 and H4,histone methylated H3K9 and H3K4 and the protein of Akt signaling pathway(Akt,p-Akt,mTOR,p-mTOR,p70S6K,p-p70S6K) were detected by Western Blot.Results(1) PHI induced a dose-dependent decrease of cells density and viability.(2) Apoptotic cells were increased after exposure to PHI with time and concentration dependent.With the augmenting of time and dose, the expression of bcL-2,caspase-9,caspase-3,McL-1,Cyt-C,XIAP were decreased.(3) PHI significantly induced an accumulation of histone acetylated H3;H4,and histone methylated H3k4 and decreased methylated H3K9.(4) The change of proteins of Akt,mT0R,p70S6K was not seen and phosphorylation of Akt(p-Akt),p70S6K(p-p70S6K),mTOR(p-mTOR) was decreased after exposure to PHI for 7 hours.The protein of Akt,p-Akt was no change after exposure to PHI for 3 hours.Conclusions(1) PHI was able to inhibit the cell growth and induce apoptosis in PC3 cells through mitochondria pathway.(2) Acetylation of histone H3,H4 was enhanced significantly,coupled to selective methylation of histone H3 lysine 4,followed with demethylation on lysine 9,of H3,which are marks of chromatin unfolding and gene transcription. (3) PHI inhibited Akt signaling pathway after 7 hours exposure,which inhibited cells growth and induced apoptosis. PHI might be a potential novel anti-prostate cancer agent.