Multiple molecular targets of indole-3-carbinol, a chemopreventive anti-estrogen in breast cancer.
The mechanism of action of the anti-estrogen indole-3-carbinol (I3C), present in cruciferous vegetables, is being examined in our laboratory with a view to promote the use of this naturally occurring chemopreventive as an alternative to synthetic anti-estrogens in human breast cancer. Our previous results clearly demonstrated that despite its low affinity for the estrogen receptor (ER), I3C abrogated estradiol-mediated cellular and biochemical effects in estradiol-responsive cells and tissues. In an earlier report, we identified ER phosphorylation as one of the targets of I3C, and in this communication we describe the consequence of inhibition of ER phosphorylation. Estradiol-induced DNA-binding proteins that bound to several DNA-responsive elements were inhibited by I3C and this effect was not at the level of DNA-protein physical interaction as inclusion of I3C in vitro in the reaction mix did not affect the binding. We analyzed the spectrum of genes induced by estradiol and modulated and/or intercepted by I3C. Our results conclude that although estradiol-mediated functions are affected by I3C, its biochemical targets are multiple and some of these may be modulated by the oligomeric products of I3C.
Ashok
B T
BT
Department of Microbiology, Immunology and Medicine, New York Medical College, Valhalla, NY 10595, USA.
Chen
Y G
YG
Liu
X
X
Garikapaty
V P S
VP
Seplowitz
R
R
Tschorn
J
J
Roy
K
K
Mittelman
A
A
Tiwari
R K
RK
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D019313:BRCA1 Protein / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002352:Carrier Proteins / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000473:pathology; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D019313:BRCA1 Protein; D002352:Carrier Proteins; D004965:Estrogen Antagonists; D007211:Indoles; C016517:indole-3-carbinol