TitleSulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects.
Publication TypeJournal Article
Year of Publication2007
AuthorsMyzak MC, Tong P, Dashwood W-M, Dashwood RH, Ho E
JournalExp Biol Med (Maywood)
Volume232
Issue2
Pagination227-34
Date Published2007 Feb
ISSN1535-3702
KeywordsAnimals, Blotting, Western, Enzyme Inhibitors, Histone Deacetylase Inhibitors, Humans, Isothiocyanates, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Thiocyanates, Transplantation, Heterologous
Abstract

Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables such as broccoli. This anticarcinogen was first identified as a potent inducer of Phase 2 enzymes, but evidence is mounting that SFN acts through other cancer chemopreventive mechanisms. We recently reported on a novel mechanism of chemoprotection by SFN in human colon cancer cells and prostate epithelial cells, namely the inhibition of histone deacetylase (HDAC). In the present investigation, we sought to test whether SFN also might inhibit HDAC activity in vivo. When consumed in the diet at an average daily dose of 7.5 mumol per animal for 21 days, SFN suppressed the growth of human PC-3 prostate cancer cells by 40% in male nude mice. There was a significant decrease in HDAC activity in the xenografts, as well as in the prostates and mononuclear blood cells (MBC), of mice treated with SFN, compared to controls. There also was a trend towards increased global histone acetylation in the xenografts, prostates, and MBC. In human subjects, a single dose of 68 g BroccoSprouts inhibited HDAC activity significantly in peripheral blood mononuclear cells (PBMC) 3 and 6 hrs following consumption. These findings provide evidence that one mechanism through which SFN acts as a cancer chemopreventive agent in vivo is through the inhibition of HDAC activity. Moreover, the data suggest that HDAC activity in PBMC may be used as a biomarker for assessing exposure to novel dietary HDAC inhibitors in human subjects.

Alternate JournalExp. Biol. Med. (Maywood)
PubMed ID17259330
PubMed Central IDPMC2267876
Grant ListP01 CA090890 / CA / NCI NIH HHS / United States
P01 CA090890-01A20003 / CA / NCI NIH HHS / United States
P30 ES00210 / ES / NIEHS 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