Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer.
BACKGROUND
Cervical cancer constitutes the second most common cancer in women. Estrogen promotes development of cervical cancer in cells infected with high risk human papillomaviruses (HPVs). We asked whether the phytochemical indole-3-carbinol (I3C) has anti-estrogenic activities in cervical cells with the goal of preventing cancer in HPV infected cells.


METHODS
Using the cervical cancer cell line CaSki, we evaluated expression of HPV and cytochrome p450 (CYP) enzymes by Northern, RNase protection or quantitative RT-PCR. I3C binding to estrogen receptor was measured by competition with estradiol. Estrogen metabolites were measured by gas chromarography-mass spectrometry (GC-MS).


RESULTS
Estradiol increased expression of HPV oncogenes whereas I3C and the estrogen metabolite 2-hydroxyestrone (2-OHE) abrogated the estrogen-increased expression of HPV oncogenes. Both I3C and 2-OHE competed with estradiol for estrogen receptor binding. I3C enhanced gene expression of CYP enzymes responsible for 2-hydroxylation of estrogen, and induced the formation of 2-OHE.


CONCLUSIONS
I3C has anti-estrogenic activities which should prevent cancer in cervical cells.
Yuan
F
F
Long Island Jewish Medical Center, Albert Einstein College of Medicine, Department of Otolaryngology, New Hyde Park, NY 11040, USA.
Chen
D Z
DZ
Liu
K
K
Sepkovic
D W
DW
Bradlow
H L
HL
Auborn
K
K
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D002584:Cervix Uteri / Q000187:drug effects* / Q000201:enzymology / Q000821:virology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006801:Humans; D006894:Hydroxyestrones / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics; D009857:Oncogenes / Q000187:drug effects; D027383:Papillomaviridae / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000201:enzymology / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology
D016588:Anticarcinogenic Agents; C068651:E6 protein, Human papillomavirus type 16; D004965:Estrogen Antagonists; D006894:Hydroxyestrones; D007211:Indoles; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012367:RNA, Viral; D011960:Receptors, Estrogen; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; C016517:indole-3-carbinol; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C024980:2-hydroxyestrone