Web site: "Information
About Herbs, Botanicals and Other Products"
URL: http://www.mskcc.org/aboutherbs
© 2003 Memorial Sloar-Kettering Cancer Center
(Monograph)
|
|
|
|
Full Text |
|
|
|
Barrie Cassileth
and K. Simon Yeung
|
|
|
Indole-3-Carbinol
(Indole-3-Methanol)
|
|
| Clinical Summary |
|
Indole-3-Carbinol
(I3C) is a specific compound found in cruciferous vegetables including
broccoli, cabbage and cauliflower. Because diets high in these vegetables
retard cancer growth in animals, I3C is thought to be a good
candidate for cancer prevention. I3C is known to stimulate detoxification
enzymes in the gut and liver. Several studies demonstrate that it can
cause cell cycle arrest and apoptosis in cancer cell lines. One placebo
controlled trial shows that I3C is effective in treating precancerous
cervical dysplasia. I3C is generally well tolerated when taken orally.
Certain studies suggest I3C may promote tumor growth in animals that have
been exposed to carcinogens, but the potential risk has never been
documented in humans. Because it may induce P450, I3C has potential
interactions with several medications.
|
|
| Scientific Name |
|
Indole-3-Methanol
|
|
| Also Known As |
|
I3C,
1H-Indole-3-methanol, indole-3-methanol, 3-(Hydroxymethyl)indole,
3-indolylcarbinol, indolylmethanol
|
|
| Brand Name |
|
I3C
Plus (Health Products Distributors)
|
|
| Food Sources |
|
Broccoli,
brussel sprouts, cabbage, cauliflower, collards, kale, kohlrabi, mustard
greens, rapeseed, rutabaga, turnip
|
|
| Purported Uses |
|
• Cancer
prevention
• Detoxification
• Viral
infections
|
|
Mechanism Of Action
[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13] |
|
I3C
is a naturally occurring compound found in cruciferous vegetables that is
known to stimulate detoxifying enzymes in the gut and liver. Many studies
indicate its potential value as a chemopreventive agent for breast cancer
through its estrogen receptor (ER) modulating effect. I3C also
down-regulates the expression of the estrogen-responsive genes pS2 and
cathepsin-D and up-regulates BRAC1. Other in vitro studies show that I3C
inhibits the expression of cycline-dependent kinase-6 and induces a G1
cell cycle arrest independent of ER signaling. There is evidence to
support the fact that I3C has a different mechanism of action than
tamoxifen and that these two substances can be used synergistically. One
randomized clinical trial suggests that I3C can increase the
2-OH-estrone:estriol metabolite ratio. This is thought to decrease the
risk of ER-sensitive breast cancer and cervical cancer. I3C can cause
apoptosis of prostate cancer cells in vitro by inhibition of Akt
activation. It also holds promise in preventing cancer with a
papillomavirus component. I3C induces cytochrome P450 1A1, which may lead
to potential drug interactions. There is some evidence from animal studies
that increases in cytochrome P450 1A1 activity also metabolizes some
environmental procarcinogens to their carcinogenic form, but this has not
been confirmed in humans.
|
|
Pharmacokinetics
[6] |
|
No
published data regarding the pharmacokinetics of I3C in humans currently
exists. Animal studies shows that I3C itself is not active. Gastric acid
converts I3C to active metabolites diindoylmethane and indolylcarbazole,
which are further metabolized in the liver. Most metabolites are excreted
through the feces.
|
|
Warnings
[5] |
|
Preliminary
evidence suggests that I3C might promote tumor growth in animals exposed
to carcinogens.
|
|
Adverse Reactions
[6], [7] |
|
I3C
is usually well tolerated when taken orally.
Reported: Some patients can experience skin rash.
|
|
Drug Interactions
|
|
Theoretically,
I3C induces cytochrome P450 1A2 and reduces serum concentration of
medications metabolized by this enzyme.
|
|
Lab Interactions
[6], [7] |
|
In
rare cases, small increases in ALT has been known to occur.
|
|
| Literature Summary And Critique |
|
Bell
MC, et al. Placebo-controlled
trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol
2000;78:123-9.
A double-blind placebo-controlled study of indole-3-Carbinol. Thirty women
with biopsy-proven cervical intraepithelial neoplasia (CIN) received
placebo, 200 or 400 mg/day of I3C for 12 weeks. None of the patients in
the placebo arm had complete regression of CIN, whereas 4 of 8 (p=0.023)
from the 200 mg/day arm and 4 of 9 (p=0.032) from the 400 mg/day arm had
complete regression after 12 weeks. The ratio of 2-hydroxyestrone to
16-alpha-hydroxyestrone changed in a dose-dependent fashion. The results
of this study show promise for the use of I3C as a nonsurgical option for
the treatment of CIN, although the data needs to be confirmed in a large
multicenter trial.
|
|
| References |
|
[1] Wattenberg
LW, Loub WD. Inhibition of polycyclic aromatic hydrocarbon-induced
neoplasia by naturally occurring indoles. Cancer Res
1978;38:1410-3.
|
|
|
[2] Bell
MC, et al. Placebo-controlled
trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol
2000;78:123-9.
|
|
|
[3] Cover
CM, et al. Indole-3-carbinol and Tamoxifen cooperate to arrest the cell
cycle of MCF-7 human breast cancer cells. Cancer Res 1999; 59:1244-51.
|
|
|
[4] Chinni
SR, Sarkar FH. Akt inactivation is a key event in
indole-3-carbinol-induced apoptosis in PC-3 cells. Clin Cancer Res
2002;8:1228-36.
|
|
|
[5]
Dashwood
RH. Indole-3-carbinol: anticarcinogen or tumor promoter in brassica
vegetables? Chem
Biol Interact
1998;110:1-5.
|
|
|
[6]
Indole-3-Carinol(I3C)
Background Information. National Toxicology Program. NIEHS
|
|
|
[7]
Wong
GY, et al. Dose-ranging study of indole-3-carbinol for breast cancer
prevention. J Cell Biochem Suppl 1997;28-29:111-6.
|
|
|
[8]
Cover
CM, et al. Indole-3-carbinol
inhibits the expression of cyclin-dependent kinase-6 and induces a G1 cell
cycle arrest of human breast cancer cells independent of estrogen receptor
signaling. J Biol Chem 1998;273:3838-47.
|
|
|
[9]
Rosen
CA, et al.Preliminary results of the use of indole-3-carbinol for
recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg
1998;118:810-5.
|
|
|
[10]
Bradlow
HL, et al. Long-term
responses of women to indole-3-carbinol or a high fiber diet. Cancer
Epidemiol Biomarkers Prev 1994;3:591-5.
|
|
|
[11]
vJin
L, et al. Indole-3-carbinol
prevents cervical cancer in human papilloma virus type 16 (HPV16)
transgenic mice. Cancer
Res
1999;59:3991-7.Jin
L, et al. Indole-3-carbinol
prevents cervical cancer in human papilloma virus type 16 (HPV16)
transgenic mice. Cancer
Res
1999;59:3991-7.vJin
L, et al. Indole-3-carbinol
prevents cervical cancer in human papilloma virus type 16 (HPV16)
transgenic mice. Cancer
Res
1999;59:3991-7.Jin
L, et al. Indole-3-carbinol
prevents cervical cancer in human papilloma virus type 16 (HPV16)
transgenic mice. Cancer
Res
1999;59:3991-7.
|
|
|
[12]
Meng
Q, et al. Indole-3-carbinol
is a negative regulator of estrogen receptor-alpha signaling in human
tumor cells. J Nutr 2000;130:2927-31.
|
|
|
[13]
Chen
DZ, et al. Indole-3-carbinol and diindolylmethane induce apoptosis of
human cervical cancer cells and in murine HPV16-transgenic preneoplastic
cervical epithelium. J
Nutr
2001;131:3294-302.
|
|
|
|
|
| Written |
|
12/13/2002 |
| Updated |
|
12/16/2002
|
|
|
|
Disclaimer: http://www.mskcc.org/mskcc/print/11790.cfm |
|
|
Source:
http://www.mskcc.org/mskcc/print/11571.cfm?RecordID=551 |
