Indole 3 Carbinol

Indole-3-carbinol or I3C is a breakdown product of the glucosinolate glucobrassicin, also known as indole-3-glucosinolate. Glucosinolates are beta-thioglucoside N-hydroxysulfates, which are primarily found in cruciferous vegetables (cabbage, broccoli sprouts, brussels sprouts, cauliflower, bok choy and kale).

Indole-3-carbinol may have cancer chemopreventive activity. Glucosinolates themselves have minimal anticancer activity. Indole-3-carbinol is produced from indole-3-glucosinolate via the action of the enzyme myrosinase (thioglucoside glucohydrolase), an enzyme which is present in cruciferous vegetables and activated upon maceration of the vegetables.

The possible anticancer activity of substances such as I3C was recognized by the Roman statesman, Cato the Elder (234-149 BC), who in his treatise on medicine wrote: "If a cancerous ulcer appears upon the breasts, apply a crushed cabbage leaf and it will make it well." Crushing a cabbage leaf would convert indole-3-glucosinolate to I3C, among other reactions.

Indole-3-carbinol may modulate estrogen metabolism. It may also have anticarcinogenic, antioxidant and anti-atherogenic activities.

The estrogen metabolites 16 alpha-hydroxyestrone and 4-hydroxyestrone have been demonstrated to be carcinogens and are thought to be responsible for the possible carcinogenic effects of estrogen. On the other hand, the estrogen metabolite 2-hydroxyestrone has been found to be protective against several types of cancer, including breast cancer. Indole-3-carbinol has been shown to increase the ratio of 2-hydroxyestrone to 16 alpha-hydroxyestrone and also to inhibit the 4-hydroxylation of estradiol. Indole-3-carbinol increases 2-hydroxylation of estrogens via induction of cytochrome P4501A1 (CYP1A1). Indole-3-carbinol is converted by stomach acid to diindolymethane (DIM) and indole (3,2,b) carbazole (ICZ). DIM and ICZ have similar activities regarding estrogen metabolism.

Regarding its possible anticarcinogenic effects, indole-3-carbinol has been shown to modulate the activities of both Phase I enzymes, such as cytochrome P4501A1, -1A2, -2B1, -2B2, -3A1 and -3A2, and Phase II enzymes, such as glutathione S-transferase (GST), quinone reductase and uridine glucuronide transferase. Indole-3-carbinol modulates the metabolism of carcinogens, such as benzo(a)pyrene, aflatoxin B1 and 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK). Indole-3-carbinol has also been shown to upregulate apoptosis in some cancer cell lines.

As mentioned above, indole-3-carbinol induces the synthesis of 2-hydroxyestrone. 2-hydroxyestrone has been found to inhibit the oxidation of low-density lipoprotein. This indicates that indole-3-carbinol has indirect antioxidant activity. 2-hydroxyestrone also appears to inhibit smooth muscle proliferation. Inhibition of smooth muscle proliferation and inhibition of the oxidation of LDL could account for the possible anti-atherogenic activity of indole-3-carbinol.

There is much unknown about the pharmacokinetics of indole-3-carbinol in humans. It is converted to DIM and ICZ by stomach acid, and DIM and ICZ are absorbed from the gastrointestinal tract. The extent of absorption of I3C, DIM and ICZ, as well as their distribution, metabolism and excretion, are currently being studied.

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LITERATURE

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