Preliminary Results of the Use of Indole‐3‐Carbinol for Recurrent Respiratory Papillomatosis

Rosen, Clark A.; Woodson, Gayle E.; Thompson, J. W.; Hengesteg, Arne; Bradlow, H. Leon

doi:10.1016/s0194-5998(98)70274-8

Cited by 138 publications

(86 citation statements)

References 18 publications

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“…In this regard, increased production of 2-hydroxyestradiol relative to 4-hydroxyestradiol and 16α-hydroxyestrone has been observed after exposure to indole 3-carbinol, a dietary micronutrient and AHR proligand. This finding is of potential clinical importance for cancer, since indole carbinols, that bind AHR as acid condensation products, are in clinical trials as cancer chemoprotective agents (Gillner et al, 1985;Malloy et al, 1997;Michnovicz et al, 1997;Telang et al, 1997;Rosen et al, 1998;Yuan et al, 1999;Bell et al, 2000)(reviewed by (Shertzer et al, 2000)). …”

Section: Effects Of Gender and Sex Hormones In The Tcdd Dose-responsementioning

confidence: 99%

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

et al. 2005

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ᮀTCDD and other polyhalogenated aromatic hydrocarbon ligands of the aryl hydrocarbon receptor (AHR) have been classically considered as non-genotoxic compounds because they fail to be directly mutagenic in either bacteria or most in vitro assay systems. They do so in spite of having repeatedly been linked to oxidative stress and to mutagenic and carcinogenic outcomes. Oxidative stress, on the other hand, has been used as a marker for the toxicity of dioxin and its congeners. We have focused this review on the connection between oxidative stress induction and the toxic effects of fetal and adult dioxin exposure, with emphasis on the large species difference in sensitivity to this agent. We examine the roles that the dioxin-inducible cytochromes P450s play in the cellular and toxicological consequences of dioxin exposure with emphasis on oxidative stress involvement. Many components of the health consequences resulting from dioxin exposure may be attributable to epigenetic mechanisms arising from prolonged reactive oxygen generation.

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Section: Effects Of Gender and Sex Hormones In The Tcdd Dose-responsementioning

confidence: 99%

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

et al. 2005

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“…I3C, which is generated by glycoside-hydrolyzing enzymes when plant cells are disrupted by processing, cooking or mastication, possesses chemopreventive properties against chemically induced tumors in rodents at a variety of sites. [11][12][13][14] Clinical pilot studies of I3C have been conducted in patients with recurrent respiratory papillomatosis 15 and cervical intraepithelial neoplasia. 16 There has also been a dose-finding study to prepare for its evaluation as a breast cancer preventive agent.…”

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confidence: 99%

Dietary agent indole‐3‐carbinol protects female rats against the hepatotoxicity of the antitumor drug ET‐743 (trabectidin) without compromising efficacy in a rat mammary carcinoma

Donald

Verschoyle

Greaves

et al. 2004

Intl Journal of Cancer

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ET-743, an experimental antitumor drug with promising activity in sarcoma, breast and ovarian carcinoma, is currently under phase 2 clinical evaluation. It is hepatotoxic in animals and patients. We tested the hypothesis that indole-3-carbinol (I3C), the hydrolysis product of glucosinolates occurring in cruciferous vegetables, may protect against ET-743-induced hepatotoxicity in the female Wistar rat, the animal species with the highest sensitivity toward the adverse hepatic effect of this drug. Hepatotoxicity was adjudged by measurement of plasma levels of bilirubin, alkaline phosphatase (ALP) and aspartate aminotransferase ( Key words: indole-3-carbinol; chemoprevention; ET-743; hepatotoxicityET-743 (ecteinascidin 743, trabectidin, Yondelis) is a tetrahydroisoquinoline alkaloid isolated from the marine tunicate Ecteinascidia turbinata. It possesses potent antineoplastic activity against a variety of human tumor xenografts grown in athymic mice, including melanoma and ovarian and breast carcinoma. [1][2][3] In clinical phase 1 studies of ET-743, promising responses were observed in patients with sarcoma, as well as breast and ovarian carcinoma, 4,5 and the drug is currently under intense investigation in a variety of phase 2 trials in cancer patients. However, myelotoxicity is dose-limiting. Furthermore, hepatotoxicity is frequently observed in the clinic, as reflected by reversible transaminitis and subclinical cholangitis, characterized by increases in alkaline phosphatase (ALP) and/or bilirubin. Treatment with ET-743 caused an increase in plasma levels of liver-specific enzymes and pathologic manifestations of cholangitis in most animal species in which it has been tested. 6,7 We recently showed that high-dose dexamethasone protects rats from ET-743-induced hepatotoxicity without compromising its antitumor activity. 8 Hepatoprotection was probably the consequence of a dramatic reduction by dexamethasone of hepatic levels of ET-743, which in turn was reasoned to be related to the ability of dexamethasone to increase the rate of metabolic detoxification of ET-743 via induction of the cytochrome P450 enzyme CYP3A in the liver. The potential use of high-dose dexamethasone as a hepatoprotectant in humans might be confounded by adverse effects, including diabetes mellitus, hypertension, arrhythmias, hypokalemia, psychosis, peptic ulceration and susceptibility to infection. 9,10 Indole-3-carbinol (I3C) is the aglycone of glucobrassicin, a microconstituent of cruciferous vegetables such as broccoli and Brussels sprouts. I3C, which is generated by glycoside-hydrolyzing enzymes when plant cells are disrupted by processing, cooking or mastication, possesses chemopreventive properties against chemically induced tumors in rodents at a variety of sites. [11][12][13][14] Clinical pilot studies of I3C have been conducted in patients with recurrent respiratory papillomatosis 15 and cervical intraepithelial neoplasia. 16 There has also been a dose-finding study to prepare for its evaluation as a breast cancer preventive agen...

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“…I3C and DIM are said to be the most popular adjunct therapies for this disorder because of their effectiveness and low level of toxicity (Auborn, 2002;Wiatrak, 2003). RRP is caused by certain types of human papilloma viruses (Coll et al, 1997;Rosen et al, 1998), and a hallmark of this disease is the tendency of the papillomas to recur after surgical removal (Gissmann et al, 1982;Kashima et al, 1996). One report indicated that most patients (55.4%) responded to the treatment of I3C/DIM by slowing down the recurrence rate, and recurrence of the disease was completely inhibited in 19% of patients (Yuan et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Activation and Potentiation of Interferon-γ Signaling by 3,3′-Diindolylmethane in MCF-7 Breast Cancer Cells

Riby

Xue²,

Chatterji³

et al. 2005

Mol Pharmacol

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3,3Ј-Diindolylmethane (DIM), a natural autolytic product in plants of the Brassica genus, including broccoli, cauliflower, and Brussels sprouts, exhibits promising cancer protective activities, especially against mammary neoplasia in animal models. We observed previously that DIM induced a G 1 cell-cycle arrest and strong induction of cell-cycle inhibitor p21 expression and promoter activity in both estrogen-responsive and -independent breast cancer cell lines. We showed recently that DIM up-regulates the expression of interferon ␥ (IFN␥) in human MCF-7 breast cancer cells. This novel effect may contribute to the anticancer effects of DIM because IFN␥ plays an important role in preventing the development of primary and transplanted tumors. In this study, we observed that DIM activated the IFN␥ signaling pathway in human breast cancer cells. DIM activated the expression of the IFN␥ receptor (IFNGR1) and IFN␥-responsive genes p56-and p69-oligoadenylate synthase (OAS). In cotreatments with IFN␥, DIM produced an additive activation of endogenous p69-OAS and of an OAS-Luc reporter and a synergistic activation of a GAS-Luc reporter. DIM synergistically augmented the IFN␥ induced phosphorylation of signal transducer and activator of transcription factor 1, further evidence of DIM activation of the IFN␥ pathway. DIM and IFN␥ produced an additive inhibition of cell proliferation and a synergistic increase in levels of major histocompatibility complex class-1 (MHC-1) expression, accompanied by increased levels of mRNAs of MHC-1-associated proteins and transporters. These results reveal novel immune activating and potentiating activities of DIM in human tumor cells that may contribute to the established effectiveness of this dietary indole against various tumors types.3,3Ј-Diindolylmethane (DIM) is a natural product formed during the autolytic breakdown of glucobrassicin present in food plants of the Brassica genus, including the common vegetables cabbage, Brussels sprouts, cauliflower, and broccoli. DIM also is produced after ingestion of indole-3-carbinol (I3C), the immediate precursor of DIM in the plants (Grose and Bjeldanes, 1992). In addition, DIM is slowly produced from I3C under near neutral pH cell culture conditions during extended incubation periods. Results of several studies indicate that DIM exhibits promising cancer-protective activities, especially against mammary neoplasia (Wattenberg and Loub, 1978;Shertzer, 1983Shertzer, , 1984. Oral intubation of I3C in a single dose before carcinogen treatment reduced the incidence and multiplicity of dimethylbenz(␣)anthracene-induced mammary tumors in rats by 70 to 80% (Wattenberg and Loub, 1978;Grubbs et al., 1995). Repeated oral administrations of DIM during the promotion stage of dimethylbenz(␣)anthracene-induced mammary tumorigenesis inhibited tumor growth in rodents by as much as 95% (Chen et al., 1998). We observed that under conventional cell culture conditions, DIM could inhibit the proliferation of breast tumor cell lines, regardless of estrogen rece...

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Preliminary Results of the Use of Indole‐3‐Carbinol for Recurrent Respiratory Papillomatosis

Cited by 138 publications

References 18 publications

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

Induction of Oxidative Stress Responses by Dioxin and other Ligands of the Aryl Hydrocarbon Receptor

Dietary agent indole‐3‐carbinol protects female rats against the hepatotoxicity of the antitumor drug ET‐743 (trabectidin) without compromising efficacy in a rat mammary carcinoma

Activation and Potentiation of Interferon-γ Signaling by 3,3′-Diindolylmethane in MCF-7 Breast Cancer Cells

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