Can indole-3-carbinol-induced changes in cervical intraepithelial neoplasia be extrapolated to other food components?

Abstract

Indole-3-carbinol (I3C) and its congener diindolylmethane (DIM) are derived from cruciferous vegetables such as broccoli and cabbage. In addition to being available in food, both I3C and DIM are available as supplements. Glucosinolates from cruciferous vegetables break down into I3C, and I3C is further converted into a range of polyaromatic derivatives, primarily DIM, which may be more effective. These and many other promising food components have anticancer properties that should do much to halt or prevent certain cancers. In animal studies, I3C/DIM not only prevents breast, endometrial, and cervical cancers (1–3) but helps prevent or ameliorate certain diseases such as recurrent respiratory papillomatosis (4) and systemic lupus erythematosus (5). A case exists for the benefits I3C/DIM for the treatment of cervical intraepithelial neoplasia (CIN) and thus potential inhibition of cervical cancer. Development of cervical cancer can be monitored because of the ease of monitoring cervical abnormalities with the Papanicolaou test (pap smear). Additional biomarkers can be included using colposcopy and tests for the presence and type of human papillomaviruses (HPVs). Abnormalities in the cervix range from a mild dyskaryosis to cancer; a percentage of these early abnormalities can progress to cancer. Infection with one of several types of HPVs is generally accepted to be a necessary step in the etiology of cervical dysplasia (6). The K14-HPV16 transgenic mouse expresses HPV oncogenes and develops cervical cancer when given estrogen chronically. The progression of the severity of cervical abnormalities to cancer in this mouse resembles that of humans (7). I3C prevents the development of cervical cancer in this transgenic mouse (3). Additionally, I3C can reduce cervical dysplasia caused by estradiol in the normal mouse (3). A small randomized controlled clinical trial in women with biopsy-confirmed highgrade cervical intraepithelial neoplasia (CIN2 and CIN3) indicated efficacy for I3C for regression of CIN (8). In addition, an investigation into the effects of DIM in a cervical randomized intervention study for cervical cytological abnormalities involving 3000 women is under way at the University of Wales College of Medicine in the United Kingdom.