TitleSulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells.
Publication TypeJournal Article
Year of Publication2006
AuthorsMyzak MC, Hardin K, Wang R, Dashwood RH, Ho E
JournalCarcinogenesis
Volume27
Issue4
Pagination811-9
Date Published2006 Apr
ISSN0143-3334
KeywordsAndrogens, Anticarcinogenic Agents, Apoptosis, Cell Cycle, Epithelial Cells, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Isothiocyanates, Male, Prostate, Prostatic Hyperplasia, Prostatic Neoplasms, Thiocyanates
Abstract

Sulforaphane (SFN), an isothiocyanate first isolated from broccoli, exhibits chemopreventive properties in prostate cancer cells through mechanisms that are poorly understood. We recently reported on a novel mechanism of chemoprotection by SFN in human colon cancer cells, namely the inhibition of histone deacetylase (HDAC). Here, we show that addition of 15 microM SFN also inhibited HDAC activity by 40, 30 and 40% in BPH-1, LnCaP and PC-3 prostate epithelial cells, respectively. The inhibition of HDAC was accompanied by a 50-100% increase in acetylated histones in all three prostate cell lines, and in BPH-1 cells treated with SFN there was enhanced interaction of acetylated histone H4 with the promoter region of the P21 gene and the bax gene. A corresponding 1.5- to 2-fold increase was seen for p21Cip1/Waf1 and Bax protein expression, consistent with previous studies using HDAC inhibitors, such as trichostatin A. The downstream events included cell cycle arrest and activation of apoptosis, as evidenced by changes in cell cycle kinetics and induction of multi-caspase activity. These findings provide new insight into the mechanisms of SFN action in benign prostate hyperplasia, androgen-dependent prostate cancer and androgen-independent prostate cancer cells, and they suggest a novel approach to chemoprotection and chemotherapy of prostate cancer through the inhibition of HDAC.

DOI10.1093/carcin/bgi265
Alternate JournalCarcinogenesis
PubMed ID16280330
PubMed Central IDPMC2276576
Grant ListP01 CA090890 / CA / NCI NIH HHS / United States
P01 CA090890-01A20003 / CA / NCI NIH HHS / United States
R01 CA080176 / CA / NCI NIH HHS / United States
CA90890 / CA / NCI NIH HHS / United States
CA80176 / CA / NCI NIH HHS / United States
CA107693 / CA / NCI NIH HHS / United States
P01 CA090890-05 / CA / NCI NIH HHS / United States
R01 CA065525 / CA / NCI NIH HHS / United States
R01 CA065525-08 / CA / NCI NIH HHS / United States
R01 CA107693 / CA / NCI NIH HHS / United States
R01 CA065525-09 / CA / NCI NIH HHS / United States
CA66525 / CA / NCI NIH HHS / United States
R01 CA080176-05 / CA / NCI NIH HHS / United States
P01 CA090890-01A29001 / CA / NCI NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States