Indole-3-carbinol: Anticarcinogen or tumor promoter in Brassica vegetables?

Department of Environmental Biochemistry, University of Hawaii, Honolulu 96822, USA.
Chemico-Biological Interactions (Impact Factor: 2.58). 04/1998; 110(1-2):1-5. DOI: 10.1016/S0009-2797(97)00115-4
Source: PubMed


Indole-3-carbinol (I3C) is one of several compounds in brassica vegetables that demonstrate anticarcinogenic effects in experimental animals. A review of Medline and CancerLit databases indicated that interest in I3C, as a cancer chemopreventive agent, has increased significantly in the past 5-10 years. Whereas most studies report inhibitory or protective effects of I3C in vivo, a few provide clear evidence for promotion or enhancement of carcinogenesis, depending upon the initiator, exposure protocol and species. In the absence of detailed information on the inhibitory and in particular, promotional mechanisms, it would seem advisable to proceed with caution before including I3C in extensive human clinical trials.

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Available from: Roderick Dashwood, Oct 07, 2015
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    • "This is in agreement with many studies reporting beneficial effects of vegetables and fruit consumption [15] [16]. Nevertheless, some animal experiments with I3C showed an increase in tumor formation after initiation with a carcinogen [17] and ICZ showed a TCDD-like inhibition of gap junction intercellular communication in vitro, indicative of a tumor promotive effect [18]. Also epidemiological studies are inconsistent as to the overall healthy effects of foods containing NAhRAs or vegetables and fruit in general [19] [20] [21]. "
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    ABSTRACT: Binding and activation of the aryl hydrocarbon receptor (AhR) is thought to be an essential step in the toxicity of the environmental pollutants dioxins and dioxin-like PCBs. However, also a number of natural compounds, referred to as NAhRAs (natural Ah-receptor agonists), which are present in, for example, fruits and vegetables, can bind and activate this receptor. To study their potential effects in humans, we first investigated the effect of the prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression in ex vivo exposed freshly isolated human lymphocytes, and compared the resulting gene expression profile with those caused by the well-known NAhRA indolo[3,2-b]carbazole (ICZ), originating from cruciferous vegetables, and by a hexane extract of NAhRA-containing grapefruit juice (GJE). Only ICZ induced a gene expression profile similar to TCDD in the lymphocytes, and both significantly up-regulated CYP1B1 and TIPARP (TCDD-inducible poly (ADP-ribose) polymerase) mRNA.Next, we performed a human intervention study with NAhRA-containing cruciferous vegetables and grapefruit juice. The expression of the prototypical AhR-responsive genes CYP1A1, CYP1B1 and NQO1 in whole blood cells and in freshly isolated lymphocytes was not significantly affected. Also enzyme activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO), as judged by caffeine metabolites in urine, were unaffected, except for a small down-regulation of NAT2 activity by grapefruit juice. Examination of blood plasma with DR CALUX® showed a 12% increased AhR agonist activity 3 and 24 h after consumption of cruciferous vegetables, but did not show a significant effect of grapefruit juice consumption. We conclude that intake of NAhRAs from food may result in minor AhR-related effects measurable in human blood and urine.
    Full-text · Dataset · May 2013
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    • "Although many studies, as discussed here, underline the chemopreventive and therapeutic properties of indole compounds against progression of human cancers, there are some reports that have actually shown opposite effects of I3C [118]. Such studies have documented different effects of I3C, ranging from no protection against progression of chemically induced carcinogenesis [119,120] to actual promotion of tumorigenesis [121-124]. "
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    ABSTRACT: Indole compounds, obtained from cruciferous vegetables, are well-known for their anti-cancer properties. In particular, indole-3-carbinol (I3C) and its dimeric product, 3,3´-diindolylmethane (DIM), have been widely investigated for their effectiveness against a number of human cancers in vitro as well as in vivo. These compounds are effective inducers of apoptosis and the accumulating evidence documenting their ability to modulate multiple cellular signaling pathways is a testimony to their pleiotropic behavior. Here we attempt to update current understanding on the various mechanisms that are responsible for the apoptosis-inducing effects by these compounds. The significance of apoptosis-induction as a desirable attribute of anti-cancer agents such as indole compounds cannot be overstated. However, an equally intriguing property of these compounds is their ability to sensitize cancer cells to standard chemotherapeutic agents. Such chemosensitizing effects of indole compounds can potentially have major clinical implications because these non-toxic compounds can reduce the toxicity and drug-resistance associated with available chemotherapies. Combinational therapy is increasingly being realized to be better than single agent therapy and, through this review article, we aim to provide a rationale behind combination of natural compounds such as indoles with conventional therapeutics.
    Full-text · Article · Dec 2011 · Cancers
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    • "could be prodrugs for cancer therapy (Chen et al., 2001; Dashwood, 1998; Edwards et al., 1999; Folkes and Wardman, 2001; Greco et al., 2002; Hong et al., 2002; Leong et al., 2001; Rossiter, 2002; Stresser et al., 1995; Wardman, 2002). BNOA has been categorised in the chemical group that demonstrated slightly acute toxicity by the Pesticide Action Network (PAN, 2009) but there are no data on its long-term effects in this site. "
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    ABSTRACT: In this study, the mutagenic and recombinogenic effects of indole-3-acetic acid (IAA), a plant growth regulator naturally synthesized in plants but produced synthetically, and β-naphthoxyacetic acid (BNOA), a synthetic plant growth regulator widely used in agricultural regions, were investigated using the somatic mutation and recombination test (SMART) in Drosophila wings. The effect of the same plant growth regulators against the proliferation and viability of a human immortalized embryonic kidney HEK293 cells which is at the early stage of carcinogenesis were also examined with MTT and trypan-blue exclusion assays. For the SMART assay, two different crosses were used: a standard and a high-bioactivation (HB) cross, involving the flare-3 and the multiple wing hairs markers. The HB cross involved flies characterized by an increased cytochrome P-450-dependent bioactivation capacity, which permits the more efficient biotransformation of promutagens and procarcinogens. In both crosses, the wings of the two types of progeny, inversion-free marker heterozygotes and balancer heterozygotes, were analyzed. The results show that IAA and BNOA are not mutagenic or recombinogenic in the wing cells of Drosophila. Furthermore, neither plant growth regulator affected the proliferation rate of HEK293 cells; however, both of them induced cell death at high concentrations.
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