Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3′-diindolylmethane and its parent compound indole-3-carbinol

Parkin, Daniel R; Malejka-Giganti, Danuta

doi:10.1016/j.cdp.2003.11.006

Cited by 26 publications

(20 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…60 The influence of DIM on AhR, as described above, results in reduced production of the carcinogenic 4-hydroxyesterone (4OHE 1 ). 61 Increased 4OHE 1 has been associated with breast tumor formation and related to initiating mutations through formation of depurinating DNA adducts. 62 DIM also induces expression of CYP3A4, 63 which, similar to CYP1A1, has been shown to influence total production of the mitogenic metabolites 4OHE 1 and 16a-hydroxyesterone (16aOHE 1 ) 64 by 2-hydroxylation of estrogens.…”

Section: Modulation Of Estrogenmentioning

confidence: 99%

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

Thomson

Ström

2016

Nutr Rev

View full text Add to dashboard Cite

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.

show abstract

Section: Modulation Of Estrogenmentioning

confidence: 99%

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

Thomson

Ström

2016

Nutr Rev

View full text Add to dashboard Cite

show abstract

“…In addition, growth of cultured human endometrial and prostate cancer cells have shown inhibition of growth with the use of DIM (19)(20)(21)(22). Animal studies with mice and rats using either cabbage, I3C, or DIM resulted in a decrease in both spontaneous and chemically induced mammary tumors, and no side effects were noted (23)(24)(25)(26)(27). A decrease in cervical dysplasia was noted in approximately 50% of the women given oral I3C, and no significant side effects were observed (28).…”

Section: Introductionmentioning

confidence: 99%

Pilot Study: Effect of 3,3′-Diindolylmethane Supplements on Urinary Hormone Metabolites in Postmenopausal Women With a History of Early-Stage Breast Cancer

Dalessandri¹,

Firestone²,

Fitch³

et al. 2004

Nutrition and Cancer

View full text Add to dashboard Cite

Dietary indoles, present in , and cortisol in the first morning urine sample before intervention and 31 days after intervention. Nineteen women completed the study, for a total of 10 in the treatment group and 9 in the placebo group. DIM-treated subjects, relative to placebo, showed a significant increase in levels of 2-OHE 1 (P = 0.020), DIM (P = 0.045), and cortisol (P = 0.039), and a nonsignificant increase of 47% in the 2-OHE 1 /16 α-OHE 1 ratio from 1.46 to 2.14 (P = 0.059). In this pilot study, DIM increased the 2-hydroxylation of estrogen urinary metabolites.

show abstract

“…Paradoxically, DIM is reported to interfere with regulation of estrogen-metabolizing CYP enzymes associated with cancer susceptibility. In this context, an interesting observation relates to DIM-mediated inhibition of a CYP complement-CYP3A1/2 activity (catalyzing 4-hydroxylation) that results in enhanced activity of hepatic microsomes to metabolize 17β-estradiol (E2) and estrone (E1) to less estrogenic 2-catechols, estrogenic 4-catechols and the 6-α, 6-β and 16α-hydroxy (OH) derivatives (Parkin and Malejka-Giganti 2004). This interesting finding suggests that DIM contributes to the formation of advanced level of 2-catechol metabolites (good estrogen), provides a crucial logical basis for attempting to prevent the tumorigenic process in estrogen-responsive sites.…”

Section: Dim and Phase-i And II Carcinogen And Xenobiotic Metabolismmentioning

confidence: 99%

Cellular, Molecular and Biological Insight into Chemopreventive and Therapeutic Potential of 3,3’-Diindolylmethane (DIM)

Banerjee

Parasramka

Sarkar

2011

Nutraceuticals and Cancer

View full text Add to dashboard Cite

Emerging evidence suggest that bioactive phytochemical is achievable by consuming moderate amount of cruciferous vegetables, such as broccoli, brussel sprouts, cauliflower and cabbage. Evaluation for chemopreventive effectiveness of these vegetables led to the identification of 3,3'-Diindolylmethane (DIM) which is generated in the acidic environment of the stomach following dimerization of Indole-3-Carbinol (I3C) monomers originating from the aforementioned class of vegetables. This article evaluates the potential targets and biological effects elicited by DIM against tumor cells to ascertain chemopreventive and therapeutic efficacy. We provide mechanistic insight into their pleiotropic action resulting in the induction of cell cycle arrest and apoptosis, and the disruption of intracellular signaling network cascade that are known to regulate angiogenesis, metastasis and invasion. The beneficial effect of DIM has been observed by preclinical in vitro and in vivo studies, suggesting that DIM could be useful as a chemopreventive agent and an adjunct to conventional therapeutics. Moreover, DIM has moved through preclinical development into clinical trials and the outcome of such investigation would likely provide definitive role of DIM in human health and diseases.

show abstract

Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3′-diindolylmethane and its parent compound indole-3-carbinol

Cited by 26 publications

References 27 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

Pilot Study: Effect of 3,3′-Diindolylmethane Supplements on Urinary Hormone Metabolites in Postmenopausal Women With a History of Early-Stage Breast Cancer

Cellular, Molecular and Biological Insight into Chemopreventive and Therapeutic Potential of 3,3’-Diindolylmethane (DIM)

Contact Info

Product

Resources

About