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 wo men. Estrogen promotes development of cervical cancer in cells infected wit h high risk human papillomaviruses (HPVs). We asked whether the phytochemic al indole-3-carbinol (I3C) has anti-estrogenic activities in cervical cells with the goal of preventing cancer in HPV infected cells. Materials and Me thods: Using the cervical cancer cell line CaSki, we evaluated expression o f HPV and cytochrome p450 (CYP) enzymes by Northern, RNase protection or qu antitative RT-PCR. I3C binding to estrogen receptor was measured by competi tion with estradiol. Estrogen metabolites were measured by gas chromarograp hy-mass spectrometry (GC-MS). Results: Estradiol increased expression of HP V oncogenes whereas I3C and the estrogen metabolite 2-hydroxyestrone (2-OHE ) abrogated the estrogen-increased expression of HPV oncogenes. Both I3C an d 2-OHE competed with estradiol for estrogen receptor binding. I3C enhanced gene expression of CW enzymes responsible for 2-hydroxylation of estrogen, and induced the formation of 2-OHE. Conclusion: I3C has anti-estrogenic ac tivities which should prevent cancer in cervical cells.