Structure elucidation of acid reaction products of indole-3-carbinol: Detection in vivo and enzyme induction in vitro

Kruif, C.A. de; Marsman, J.W.; Venekamp, J.C.; Falke, H.E.; Noordhoek, J.; Blaauboer, Bas J.; Wortelboer, Heleen M.

doi:10.1016/0009-2797(91)90090-t

Cited by 162 publications

(109 citation statements)

References 19 publications

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“…In fact, a pH-dependent, acid-catalyzed condensation rapidly converts I3C to oligomers that include DIM, which is the major indole bioactive compound, accounting for an estimated 60% of the I3C end product. 23 As the conversion is pH dependent, exposure to stomach acid is necessary for the conversion of I3C into DIM 22 and other acid condensation products. In experimental models, I3C has been shown to self-condense to produce DIM at a ratio of 2:1.…”

Section: Metabolism Of Diindolylmethane From Indole-3-carbinolmentioning

confidence: 99%

Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies

Thomson

Ström

2016

Nutr Rev

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Diet is a modifiable factor associated with the risk of several cancers, with convincing evidence showing a link between diet and breast cancer. The role of bioactive compounds of food origin, including those found in cruciferous vegetables, is an active area of research in cancer chemoprevention. This review focuses on 3,3 0 -diindolylmethane (DIM), the major bioactive indole in crucifers. Research of the cancerpreventive activity of DIM has yielded basic mechanistic, animal, and human trial data. Further, this body of evidence is largely supported by observational studies. Bioactive DIM has demonstrated chemopreventive activity in all stages of breast cancer carcinogenesis. This review describes current evidence related to the metabolism and mechanisms of DIM involved in the prevention of breast cancer. Importantly, this review also focuses on current evidence from human observational and intervention trials that have contributed to a greater understanding of exposure estimates that will inform recommendations for DIM intake.

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Section: Metabolism Of Diindolylmethane From Indole-3-carbinolmentioning

confidence: 99%

Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies

Thomson

Ström

2016

Nutr Rev

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“…When I3C is exposed to gastric acid it is converted to a number of self-condensation products, the major one of which is 3,3 0 -diindolylmethane (DIM) (14,15) . DIM is readily detected in the liver and faeces of rodents fed on I3C, whereas the ingested I3C is not detected in these animals (16) .…”

Section: Constituents Of Cruciferous Vegetables and Mechanisms Of Thementioning

confidence: 99%

Cruciferous vegetable intake and the risk of human cancer: epidemiological evidence

Kim

Park

2008

Proc. Nutr. Soc.

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Over several decades a number of epidemiological studies have identified the inverse associations between cruciferous vegetables and the risk of several cancers, including gastric, breast, colo-rectal, lung, prostate, bladder and endometrial cancers, via plausible physiological mechanisms. Although retrospective case-control studies have consistently reported inverse associations between the risk of these cancers and the intake of cruciferous vegetables and isothiocyanate-containing plants, current prospective cohort studies have found these associations to be weaker and less consistent. Genetic variations affecting the metabolism of glucosinolate hydrolysis products may modulate the effects of cruciferous vegetable consumption on cancer risk, which may be one of the reasons for the discrepancies between retrospective and prospective studies. In addition, methodological issues such as measurement errors of dietary exposure, misclassification, recall bias, publication bias, confounding and study design should be carefully considered in interpreting the results of case-control and cohort studies and in drawing conclusions in relation to the potential effects of cruciferous vegetables on cancers. Although recent comprehensive reviews of numerous studies have purported to show the specific protective role of cruciferous vegetables, and particularly Brassicas, against cancer risk, the current epidemiological evidence suggests that cruciferous vegetable consumption may reduce the risk only of gastric and lung cancers. However, there is at present no conclusive evidence that the consumption of cruciferous vegetables attenuates the risk of all other cancers.

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“…DIM (3,3′-diindolylmethane) is produced in the stomach after ingestion of vegetables of the Brassica family, such as broccoli, cauliflower and Brussels' sprouts, which contain large amounts of indole-3-carbinol (I3C). In the stomach, I3C is converted via acid-catalyzed reactions to various condensation products, including what is considered to be its most biologically active metabolite, DIM [6,7]. Current evidence indicates that DIM acts as an anticancer agent as it inhibits the growth of a multitude of cancer cell types in vitro and in vivo [8,9] and has produced positive responses in clinical trials for the treatment of prostate cancer when applied as an absorption-enhanced formulation [10].…”

Section: Introductionmentioning

confidence: 99%

Ring-substituted analogs of 3,3′-diindolylmethane (DIM) induce apoptosis and necrosis in androgen-dependent and –independent prostate cancer cells

et al. 2013

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SummaryWe recently reported that novel ring-substituted analogs of 3,3′-diindolylmethane (ring-DIMs) have anti-androgenic and growth inhibitory effects in androgen-dependent prostate cancer cells. The objectives of this study were to confirm the ability of 4,4′-and 7,7′-dibromo-and dichlorosubstituted ring-DIMs to inhibit androgen-stimulated proliferation of androgen-dependent LNCaP human prostate cancer cells using a non-invasive, real-time monitoring technique. In addition, their ability to induce apoptotic and necrotic cell death in androgen-dependent as well asindependent (PC-3) prostate cancer cells was studied. Prostate cancer cells were treated with increasing concentrations of DIM and ring-DIMs (0.3-30 μM) and effects on cell proliferation were measured in real-time using an xCELLigence cellular analysis system. Chromatin condensation and loss of membrane integrity were determined by Hoechst and propidium iodide staining, respectively. Apoptotic protein markers were measured by immuno-blotting and activation of caspases determined using selective fluorogenic substrates. Intra-and extracellular concentrations of DIM and ring-DIMs were assessed by electrospray ionization tandem mass CIHR Author ManuscriptCIHR Author Manuscript CIHR Author Manuscript spectrometry. Ring-DIMs inhibited androgen-stimulated LNCaP cell proliferation and induced apoptosis and necrosis in LNCaP and PC-3 cells with 2-4 fold greater potencies than DIM. DIM and the ring-DIMs increased caspases −3, −8 and −9 activity, elevated expression of Fas, FasL, DR4 and DR5 protein, and induced PARP cleavage in both cell lines. The cytotoxicity of the most potent ring-DIM, 4,4′-dibromoDIM, but not the other compounds was decreased by an inhibitor of caspase −3. The 4,4′-dibromoDIM was primarily found in the extracellular medium, whereas all other compounds were present to a much larger extent in the cell. In conclusion, ring-DIMs inhibited prostate cancer cell growth and induced cell death in LNCaP and PC-3 cells with greater potencies than DIM; they also structure-dependently activated different cell death pathways suggesting that these compounds have clinical potential as chemopreventive and chemotherapeutic agents in prostate cancer, regardless of hormone-dependency.

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Structure elucidation of acid reaction products of indole-3-carbinol: Detection in vivo and enzyme induction in vitro

Cited by 162 publications

References 19 publications

Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies

Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies

Cruciferous vegetable intake and the risk of human cancer: epidemiological evidence

Ring-substituted analogs of 3,3′-diindolylmethane (DIM) induce apoptosis and necrosis in androgen-dependent and –independent prostate cancer cells

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