Dialyl-sulfide with chalcone prevent breast cancer promoting SULT1E1
malregulations and oxidant-stress dependant HIF1a-MMPs induction.
Abstract
Background: In some breast cancers, decreased estrogen-sulfotransferase
(SULT1E1) and its inactivation caused by oxidative-stress lead to
elevated E2 levels as well as hypoxia-inducible tissue-damaging factors.
Methods: Here, matrix-metalloproteases (MMP2/9) activity and
SULT1E1-HIF1α protein/gene expression (Western-blot/RTPCR) were assessed
in human breast-cancers versus their adjacent-tissues. Oxidant-stress
neutralizer, chalcone (α,β unsaturated ketone) and SULT1E1-inducer
dialyl-sulfide (source garlic; Allium sativum) were tested to prevent
cancer causing factors in rat, in-vitro and in-vivo model. The
antioxidant-enzymres SOD1, catalase, GPx and LDH, and
matrix-degenerating MMP2/9 activities were assessed (gel-zymogram).
Histoarchitecture (HE-staining) and tissue SULT1E1-localization
(immuno-histochemistry) were screened. Extensive statistical-analysis
were performed. Results: Human cancer-tissue expresses higher SULT1E1,
paralleling HIF1α protein/mRNA owing to lower LDH activity. In addition,
increase of MMP2/9 activities commenced tissue damage. However, chalcone
and DAS significantly induced SULT1E1 gene/protein, and suppressed HIF1α
expression, and MMP2/9 activities in rat tissues. Correlation of
individual parameter statistics and group statistics of t-test suggest
significant correlation of oxidative-stress (MDA) with SULT1E1
(p=0.006), HIF1α (p=0.006) protein-expression. The NPSH showed a
negative correlation (p=0.001) with HIF1α, These two proteins and
SULT1E1 mRNA expressions in human breast tumor were significantly higher
(p<0.05) compared to the adjacent tissues. Pearson correlation
data suggest, SULT1E1 is correlated with NPSH in different exposure
groups. Conclusions: Breast cancers associate with SULT1E1, HIF1α and
MMPs deregulations. Higher SULT1E1-protein in advanced cancer, remain
inactive in oxidant oxidative environment and may be re-activated in
chalcone induced reducing-state. Moreover, DAS induced SULT1E1 mRNA
expression augments its protein increment. Synergistic drug-effects
commenced HIF1α and MMPs suppression. Further studies are necessary.