Cancer Research Institute, Slovak Academy of Sciences

marker, phosphorylated histone H3 staining as a marker of mitotic arrest was enhance in the
kale sprout group. Also, we observed an increase in histone H4 acetylation, which we could
not link to an inhibition of HDAC activity, but which might be involved in up-regulation
of p21 mRNA and protein expression. Interestingly, hemoglobin levels in tumor cell lysate
and vessels in tumor sections were significantly reduced by consuming kale sprout powder,
indicating anti-angiogenic potential. This was associated with down-regulated VEGF-c
expression.
In conclusion, our study indicate that the combination of components in kale
sprouts affect both pro-proliferative (hormone signaling) and anti-proliferative mechanisms
(histone H4 acetylation, cell cycle arrest, anti-angiogenesis), which may abrogate their
effect on tumor growth. These results may contribute to a better understanding of the effects
of cruciferous vegetable consumption in cancer prevention.
Pappa et al., Quantitative combination effects between sulforaphane and 3,3’-diindolylmethane on proliferation
of human colon cancer cells in vitro. Carcinogenesis 28, 1471-1477 (2007)
L7
NOVEL TARGETS OF DIETARY ISOTHIOCYANATES IN CANCER
PREVENTION
Bao, Y.
School of Medicine, Health Policy and Practice,University of East Anglia, UK
y.bao@uea.ac.uk
Epidemiological studies suggest that a diet rich in cruciferous vegetables is
associated with a decreased risk of many common cancers. Their protective effects are
attributed, at least in part, to isothiocyaniates, the breakdown products of glucosinolates.
Many studies have demonstrated that isothiocyanates can modulate multiple cellular
targets including phase I carcinogen-activating enzymes, phase II detoxification enzymes,
cell cycle arrest and apoptosis.
Recent studies suggest that sulforaphane can upregulate sequestosome p62 and
induce autophagy (cellular self-eating). p62 is a common component of protein aggregates
associated with protein misfolding diseases and play an important role in the life and death
decisions of the cell. Interestingly, we have shown that sulforaphane can induce Nrf2 translocation
into nucleus and increase p62 expression in human hepatocytes. Therefore, we
speculate that this stimulation of the Nrf2 pathway by sulforaphane and consequent increase
in p62 could facilitate targeting of damaged cellular components to autophagosomes and
play a role in cancer prevention.
Furthermore, we have shown that sulforaphane can down-regulate COX-2
expression in colon and bladder cancer cells. Moreover, we have established that
synergistic interactions occur between isothiocyanates and mineral selenium in the
regulation of antioxidant gene expression including thioredoxin reductase (TR1) and
gastrointestinal glutathione peroxidase (GI-GPx).
Very recently, we have found that sulforaphane down-regulated the expression
of serotonin receptors and serotonin reuptake transporter (SERT), promoting signals for
serotonin release by mediating G-proteins and activating neurotransmitter receptors, which
are important in the proliferation of colon cancer cells.
In summary, the effect of sulforaphane on the expression of p62, COX-2 and
neurotransmitter receptors may provide new insights into the development of strategies that
utilize dietary isothiocyanates for cancer prevention.
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