RESUMO
Objective To investigate phenyhexyle isothiocyanate (PHI) modulating histone acetylation and inhibiting Akt signaling pathway in prostate cancer cell line PC3 in vitro. Methods Apoptotic cells were measured by TUNEL assay. Histone acetylated H3, H4 and the Akt protein signaling pathway (Akt, p-Akt, mTOR, p-mTOR, p70S6K and p-p70S6K) were detected by Western blot. Results Apoptotic cells increased after exposure to PHI with concentration dependent. PHI significantly induced an accumulation of histone acetylated H3, H4. The change of Akt, mTOR, p70S6K proteins was not observed. Phosphorylation of Akt (p- Akt), mTOR (p-mTOR) and p70S6K (p-p70S6K) decreased after exposure to PHI for 7 h. Conclusions PHI can induce histone acetylation H3, H4 accumulation. PHI inhibits Akt signaling pathway resulting cell apoptosis. It might be a new anticancer agent.
RESUMO
Objective To investigate the effect of phenylhexyle isothiocyanate (PHI) on demethylation and activation of transcription gene p15 in acute leukemia cell line Molt-4. Methods DNA sequencing and modified methylation specific PCR (MSP) were used to screen p15-M and p15-U mRNA after Moh-4 cells were treated with PHI. P15 mRNA was measured by RT-PCR. Pl5 protein was detected by Western blotting. Results Hypermethylation of gene pl5 was apparently attenuated and activation of transcription p15 gene was de novo after 5 days exposure to PHI. PHI enhanced both the expression of p15 mRNA and p15 protein in a concentration-dependent manner. The ratio of the gray scale of p15 mRNA strap was 0.17±0.12 in control, 0.29±0.14 in PHI 10 μmol/L, 0.55±0.07 in PHI 20 μmol/L, 0.93±0.13 in PHI 40 μmol/L. Conclusion PHI could active demethylation and transcription of gene p15.