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ISS
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Sulforaphane
inhibits histone deacetylase activity in BPH-1, LnCaP, and PC-3 prostate
epithelial cells.
Carcinogenesis. 2005 Nov 9
Myzak MC, Hardin K, Wang R, Dashwood RH, Ho E.
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331; Molecular
and Cellular Biology Program, Oregon State University, Corvallis, OR 97331.
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 p21(Cip1/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.
Note from ISS: Several crucifer sprouts
including broccoli sprouts are currently the most potent natural source of
sulforaphane known. They often produce 10 to 100 times the amount of
sulforaphane as their corresponding mature vegetables.
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