Potent HAT Inhibitory Effect of Aqueous Extract from Bellflower(platycodon grandiflorum) Roots on Androgen Receptor-mediated Transcriptional Regulation

Abstract

Histone acetyltransferase (HAT) is a family of enzymes that regulate histone acetylation. Dysfunction of HAT plays a critical role in the development of cancer. Here we have screened the various plant extracts to find out the potent HAT inhibitors. The bellflower(platycodon grandiflorum) root have exhibited approximately 30% of the inhibitory effects on HAT activity, especially p300 and CBP (CREB-binding protein) at the concentration of 100 μg/mL. The cell viability was decreased approximately 52% in LNCaP cell for 48 hr incubation. Furthermore, mRNA level of 3 androgen receptor target genes, PSA, NKX3.1, and TSC22 were decreased with bellflower root extract treatment (100 μg/mL) in the presence of androgen. In ChIP assay, the acetylation of histone H3 and H4 in PSA promoter region was dramatically repressed by bellflower root treatment, but not TR target gene, D1. Therefore, the potent HAT inhibitory effect of bellflower root led to the decreased transcription of AR target genes and prostate cancer cell growth with the repression of histone hyperacetylation.