Yuan F, Chen D Z, Liu K, Sepkovic D W, Bradlow H L, Auborn K
Long Island Jewish Medical Center, Albert Einstein College of Medicine, Department of Otolaryngology, New Hyde Park, NY 11040, USA.
Anticancer Res. 1999 May-Jun;19(3A):1673-80.
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.
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).
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.
I3C has anti-estrogenic activities which should prevent cancer in cervical cells.
宫颈癌是女性第二常见的癌症。雌激素会促进高危型人乳头瘤病毒(HPV)感染细胞中宫颈癌的发展。我们研究了植物化学物质吲哚 - 3 - 甲醇(I3C)在宫颈细胞中是否具有抗雌激素活性,目的是预防HPV感染细胞中的癌症。
使用宫颈癌细胞系CaSki,我们通过Northern印迹、核糖核酸酶保护或定量逆转录聚合酶链反应(RT-PCR)评估HPV和细胞色素P450(CYP)酶的表达。通过与雌二醇竞争来测量I3C与雌激素受体的结合。通过气相色谱 - 质谱联用(GC-MS)测量雌激素代谢物。
雌二醇增加了HPV癌基因的表达,而I3C和雌激素代谢物2 - 羟基雌酮(2 - OHE)消除了雌激素增加的HPV癌基因表达。I3C和2 - OHE都与雌二醇竞争雌激素受体结合。I3C增强了负责雌激素2 - 羟化的CYP酶的基因表达,并诱导了2 - OHE的形成。
I3C具有抗雌激素活性,应能预防宫颈细胞中的癌症。