Protection by chlorophyllin and indole-3-carbinol against 2-amino-1-methyl-6-phenylimidazo[4,5-<i>b</i>]pyridine (PhIP)-induced DNA adducts and colonic aberrant crypts in the F344 rat

Guo, Dexin; Schut, Herman A.J.; Davis, Cindy D.; Snyderwine, Elizabeth G.; Bailey, George S.; Dashwood, Roderick H.

doi:10.1093/carcin/16.12.2931

Cited by 111 publications

(54 citation statements)

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“…When administered before or at the same time as the carcinogen, oral I3C has been found to inhibit the development of cancer in a variety of animal models and tissues, including cancers of the mammary gland (breast) [131,132], stomach [133], colon [134,135], lung [136] and liver [137]. However, a number of studies found that I3C actually promoted or enhanced the development of cancer when administered chronically after the carcinogen (post initiation).…”

Section: Adverse Effectsmentioning

confidence: 99%

Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis

Higdon

Delage

Williams

et al. 2007

Pharmacological Research

910

697

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Cruciferous vegetables are a rich source of glucosinolates and their hydrolysis products, including indoles and isothiocyanates, and high intake of cruciferous vegetables has been associated with lower risk of lung and colorectal cancer in some epidemiological studies. Glucosinolate hydrolysis products alter the metabolism or activity of sex hormones in ways that could inhibit the development of hormone-sensitive cancers, but evidence of an inverse association between cruciferous vegetable intake and breast or prostate cancer in humans is limited and inconsistent. Organizations such as the National Cancer Institute recommend the consumption of 5-9 servings of fruits and vegetables daily, but separate recommendations for cruciferous vegetables have not been established. Isothiocyanates and indoles derived from the hydrolysis of glucosinolates, such as sulforaphane and indole-3-carbinol (I3C), have been implicated in a variety of anticarcinogenic mechanisms, but deleterious effects also have been reported in some experimental protocols, including tumor promotion over prolonged periods of exposure. Epidemiological studies indicate that human exposure to isothiocyanates and indoles through cruciferous vegetable consumption may decrease cancer risk, but the protective effects may be influenced by individual genetic variation (polymorphisms) in the metabolism and elimination of isothiocyanates from the body. Cooking procedures also affect the bioavailability and intake of glucosinolates and their derivatives. Supplementation with I3C or the related dimer 3,3′-diindolylmethane (DIM) alters urinary estrogen metabolite profiles in women, but the effects of I3C and DIM on breast cancer risk are not known. Small preliminary trials in humans suggest that I3C supplementation may be beneficial in treating conditions related to human papilloma virus infection, such as cervical intraepithelial neoplasia and recurrent respiratory papillomatosis, but larger randomized controlled trials are needed.

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Section: Adverse Effectsmentioning

confidence: 99%

Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis

Higdon

Delage

Williams

et al. 2007

Pharmacological Research

910

697

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“…[79][80][81][82][83][84][85] Shertzer's group showed that I3C protected against covalent binding of benzo[a]pyrene metabolites to mouse liver DNA and protein. 82 They examined the relationship between the ability of I3C to alter the activity of hepatic AHH, and its ability to inhibit the covalent binding of benzo [a] pyrene (BaP) metabolites to DNA and protein.…”

Section: I3c Prevents Carcinogen-dna Adduct Formationmentioning

confidence: 99%

“…Guo and colleagues showed protection by chlorophyllin and I3C PhIPinduced DNA adducts and aberrant colonic crypts in the F344 rat. 83 During weeks 3 and 4 of a 16-week study, F344 rats were given PhIP by oral gavage (50 mg/kg body weight, alternating days). Inhibitors were given either before and during PhIP exposure, after PhIP treatment, or continuously for 16 weeks.…”

Section: I3c Inhibits Tumor Growth Invasion and Angiogenesis In Animalsmentioning

confidence: 99%

Molecular Targets and Anticancer Potential of Indole-3-Carbinol and Its Derivatives

2005

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Previously published online as a Cell Cycle E-publication: http://www.landesbioscience.com/journals/cc/abstract.php?id=1993 KEY WORDSI3C ReviewMolecular Targets and Anticancer Potential of Indole-3-Carbinol and Its Derivatives ABSTRACT Indole-3-carbinol (I3C) is produced by members of the family Cruciferae, and particularly members of the genus Brassica (e.g., cabbage, radishes, cauliflower, broccoli, Brussels sprouts, and daikon). Under acidic conditions, I3C is converted to a series of oligomeric products (among which 3,3'-diindolylmethane is a major component) thought to be responsible for its biological effects in vivo. In vitro, I3C has been shown to suppress the proliferation of various tumor cells including breast cancer, prostate cancer, endometrial cancer, colon cancer and leukemic cells; induce G 1 /S arrest of the cell cycle and induce apoptosis. The cell cycle arrest involves downregulation of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4 and CDK6 and upregulation of p15, p21 and p27. Apoptosis by I3C involves downregulation antiapoptotic gene products, including Bcl-2, Bcl-xL, survivin, inhibitor-of-apoptosis protein (IAP), X chromosome-linked IAP (XIAP), and Fas-associated death domain protein-like interleukin-1-β-converting enzyme inhibitory protein (FLIP); upregulation of proapoptotic protein Bax; release of micochondrial cytochrome C; and activation of caspase-9 and caspase-3. This agent inhibits the activation of various transcription factors including nuclear factor-kappaB, SP1, estrogen receptor, androgen receptor and nuclear factor-E2-related factor 2 (Nrf2). This indole potentiates the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) through induction of death receptors and synergises with chemotherapeutic agents through downregulation of P-glycoprotein (P-gp). In vivo, I3C was found to be a potent chemopreventive agent for hormonal-dependent cancers such as breast and cervical cancer. These effects are mediated through its ability to induce apoptosis, inhibit DNA-carcinogen adduct formation, and suppress free-radical production, stimulate 2-hydroxylation of estradiol, inhibit invasion and angiogenesis. Numerous studies have indicated that I3C also has a strong hepatoprotective activity against various carcinogens. Initial clinical trials in women have shown that I3C is a promising agent against breast and cervical cancers.

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“…I3C has also been examined as a potential chemopreventive agent and has been shown to be effective in a wide variety of carcinogen-induced tumor models (6)(7)(8)(9). It has been proposed that the efficacy of many of the so-called blocking agents, such as 5,6-BF or I3C, on cancers initiated by procarcinogens (DMBA, aflatoxin, etc.)…”

Section: Introductionmentioning

confidence: 99%

Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: Is DIM a substitute for I3C?

Lubet¹,

Heckman²,

Flora³

et al. 2011

Oncol Rep

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Abstract. the abilities of 5,6-benzoflavone (5,6-BF, a synthetic flavonoid), indole-3-carbinol (I3C, a plant derived product) or diindolylmethane (DIM, a condensation product of I3C) to alter the induction of mammary cancers induced by the carcinogens 7,12-dimethylbenzanthracene (DMBA) or N-methyl-N-nitrosourea (MNU) were evaluated. Interestingly, the first two agents act as aryl hydrocarbon receptor (AhR) agonists, while DIM does not. The agents were initially examined for their ability to inhibit DMBA-induced mammary carcinogenesis. Agents were administered for 14 days starting 7 days prior to a single dose of the carcinogen. Evaluated over an extensive range of doses (165, 550 and 1650 ppm in the diet), 5,6-BF caused a dose-dependent decrease of mammary cancers. In addition, 5,6-BF at doses of 1650 and 165 ppm in the diet blocked the induction of DMBA-induced DNA adducts in the mammary gland by approximately 85% and 45%, respectively. In contrast, DIM (180 or 20 mg/kg BW/day) failed to block induction of DMBA tumors. The effect of these agents on the promotion/progression phase of carcinogenesis using the MNU mammary cancer model was also determined. 5,6-BF (1650 or 165 ppm in the diet), I3C (180 or 60 mg/kg BW/day administered by gavage), or DIM (180 or 60 mg/kg BW/day by gavage) were initiated 5 days after the administration of MNU, and continually thereafter. 5,6-BF decreased MNUinduced mammary tumor multiplicity by 40-60%. I3C reduced tumor multiplicity at the high dose, while DIM at either dose had minimal effects on tumor multiplicity. Thus, 5,6-BF and I3C were highly effective against initiation of DMBA-induced mammary carcinogenesis, and were also effective against MNU-induced tumors during the promotion/progression phase of carcinogenesis. In contrast, DIM had minimal effects in either model; arguing that administration of DIM is not analogous to administration of I3C.

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Protection by chlorophyllin and indole-3-carbinol against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced DNA adducts and colonic aberrant crypts in the F344 rat

Cited by 111 publications

References 0 publications

Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis

Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis

Molecular Targets and Anticancer Potential of Indole-3-Carbinol and Its Derivatives

Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: Is DIM a substitute for I3C?

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