Multifunctional Aspects of the Action of Indole‐3‐Carbinol as an Antitumor Agent

Abstract

Previous studies from this laboratory have suggested that 2-hydroxyestrone is protective against breast cancer, whereas the other principal metabolite, 16 alpha-hydroxyestrone, and the lesser metabolite quantitatively, 4-hydroxyestrone, are potent carcinogens. Attempts to directly decrease the formation of the 16-hydroxylated metabolite were either unsuccessful or required such high levels of the therapeutic agent as to be impractical. On the other hand the concentration of the protective metabolite, 2-hydroxyestrone, proved to be readily modulated by a variety of agents, both in the direction of increased protection and the opposite direction, increased risk by a variety of agents and activities. We have focussed our attention on indole-3-carbinol, a compound found in cruciferous vegetables, and its further metabolites in the body, diindolylmethane (DIM) and indolylcarbazole (ICZ), because of its relative safety and multifaceted activities. It has been shown that it induces CyP4501A1, increasing 2-hydroxylation of estrogens, leading to the protective 2-OHE1, and also decreases CyP1B1 sharply, inhibiting 4-hydroxylation of estradiol, thereby decreasing the formation of the carcinogenic 4-OHE1. In addition to these indirect effects as a result of altered estrogen metabolism, indole-3-carbinol has been shown to have direct effects on apoptosis and cyclin D, resulting in blockage of the cell cycle. In addition to its antitumor activity in animals, it has also been shown to be effective against HPV-mediated tumors in human patients. All of these responses make the study of its behavior as a therapeutic agent of considerable interest.

Genome‐wide identification of glucosinolate synthesis genes inBrassica rapa

“…Indole-3-carbinol, a derivative of glucobrassicin, also comprises a good anticarcinogen. Both exhibit their effects by inducing phase II detoxification enzymes, altering estrogen metabolism, blocking the cell cycle or protecting against oxidative damages [11][12][13][14][15]. Phenethyl isothiocyanate, a derivative of gluconasturtiin, was reported to be effective for chemoprotection [16][17][18], although it possesses genotoxic activity [19][20][21].…”

Effects of indole-3-carbinol on metabolic parameters and on lipogenesis and lipolysis in adipocytes 182

“…Having a sustained oestrogen modifying effect I3C is a good candidate for clinical trials in women at an increased risk of developing breast cancer (Brignall, 2001). In addition to these indirect effects as a result of altered oestrogen metabolism, indole-3-carbinol as well as DIM has been shown to have direct effects on apoptosis and cyclin D, resulting in blockage of the cell cycle (Bradlow et al, 1999). Because it facilitates the inactivation of oestrogen, it is possible that I3C might tend to promote osteoporosis in postmenopausal women and could interfere with oestrogen therapies (birth control pills and hormone replacement therapy).…”

Human papillomavirus, cervical carcinogenesis and chemoprevention with Indole derivates – a review of pathomechanisms

“…3). 2-hydroxy-oestradiol is anti-oestrogenic and anti-proliferative, whereas 16a-hydroxy-oestrone and 4-hydroxy-oestrone cause cell proliferation and have carcinogenic potential (see reviews in [89,90]). …”