Methyl‐substituted diindolylmethanes as inhibitors of estrogen‐induced growth of T47D cells and mammary tumors in rats

McDougal, Andrew; Gupta, Mona; Morrow, Derek; Ramamoorthy, K.; Lee, Jeong‐Eun; Safe, Stephen

doi:10.1023/a:1010608000074

Cited by 71 publications

(56 citation statements)

References 26 publications

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“…All experiments were performed in triplicate and results are presented as mean+standard error of mean (6+s.e.m.) DIM components, which are reported to exhibit anticarcinogenic activity in vitro and in experimental models of mammary tumors (Kojima et al, 1994;McDougal et al, 2001;Morse et al, 1990;Stoewsand et al, 1988;Wattenberg and Loub, 1978). We Figure 6 The in vitro effects of TCDD on pancreatic cancer cell growth as described in Materials and methods.…”

Section: Discussionmentioning

confidence: 99%

Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer

et al. 2002

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The arylhydrocarbon receptor (AhR) was initially identified as a member of the adaptive metabolic and toxic response pathway to polycyclic aromatic hydrocarbons and to halogenated dibenzo-p-dioxins and dibenzofurans. In the present study, we sought to determine the functional significance of the AhR pathway in pancreatic carcinogenesis. AhR expression was analysed by Northern blotting. The exact site of AhR expression was analysed by in situ hybridization and immunohistochemistry. The effects of TCDD and four selective AhR agonists on pancreatic cancer cell lines were investigated by growth assays, apoptosis assays, and induction of the cyclin-dependent kinase inhibitor p21. There was strong AhR mRNA expression in 14 out of 15 pancreatic cancer samples, weak expression in chronic pancreatitis tissues, and faint expression in all normal pancreata. In pancreatic cancer tissues, AhR mRNA and protein expression were localized in the cytoplasm of pancreatic cancer cells. TCDD and the four AhR agonists inhibited pancreatic cancer cell growth in a dose-dependent manner, and decreased anchorage-independent cell growth. DAPI staining did not reveal nuclear fragmentation and CYP1A1 and was not induced by TCDD and AhR agonists. In contrast, TCDD and AhR agonists induced the expression of the cyclindependent kinase inhibitor p21. In conclusion, the relatively non-toxic AhR agonists caused growth inhibition in pancreatic cancer cells with high AhR expression levels via cell cycle arrest. In addition, almost all human pancreatic cancer tissues expressed this receptor at high levels, suggesting that these or related compounds may play a role in the therapy of pancreatic cancer in the future.

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Section: Discussionmentioning

confidence: 99%

Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer

et al. 2002

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“…4,6,[35][36][37][38][39][40][41][42][43][44][45][46][47] Liu's group, for example, showed that ICZ exhibits both antiestrogenic and estrogenic activity. 44 I3C and its acid-derived condensation product, ICZ, bound to the aryl hydrocarbon (Ah) receptor and induced cytochrome p450 (CYP)1A1/1A2 gene expression in both in vivo and in vitro models.…”

Section: I3c Modulates the Estrogen Receptormentioning

confidence: 99%

“…4 Their study demonstrated that methyl-substituted DIMs are selective AhR modulators (SAhRMs) with potential for clinical treatment of breast cancer.…”

Section: I3c Modulates the Estrogen Receptormentioning

confidence: 99%

“…Methylsubstituted DIMs include 1,1'-dimethyl-, 2,2'-dimethyl-, 5,5'-dimethyl-, 6,6'-dimethyl-, and 7,7'-dimethyl DIM and 1,1',2,2'-tetramethylDIM. 4 Other analogues of I3C include indole-3-acetonitrile, indolo [3,2-b]carbazole (ICZ), and, indole-3-carboxaldehyde. 5 Chang et al using a cell proliferation assay in human MCF-7 cells, showed that 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr-1) is a major antiproliferative component that can suppress the proliferation of both estrogen receptor (ER) positive and ER negative cells.…”

Section: Introductionmentioning

confidence: 99%

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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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“…3,3'-arylmethylene bis-1H-Indole and its derivatives are well known and an important class of heterocyclic compounds which are used in pharmaceuticals as bioactive intermediates, agrochemicals and in material science. 1 They exhibit a broad spectrum of biological activities such as antimicrobial and antifungal, 2 antibacterial, 3 antitumor, 4 and antioxidantetc agents. 5 Recently, bis (5-methoxy-3-indolyl) methanes have been used as DNA-based electrochemical biosensors that considerably reduce the growth of cancer cell lines such as HOP-92 (lung), A498 (renal), and MDAMB-231/ITCC (breast).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of Polyindole and its catalytic performance study as a heterogeneous catalyst

et al. 2016

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Abstract. The catalytic performance study of polyindole as a heterogeneous catalyst is reported for the synthesis of 3,3'-arylmethylene-bis-1H-Indole derivatives using various substituted aldehydes and indole under reflux reaction condition with good to excellent yield. Polyindole was synthesized by chemical oxidative polymerization using citric acid as a dopant. The synthesized polymer was well characterized by various spectroscopic techniques like FT-IR, XRD, FESEM, etc. The XRD pattern confirms the partially crystalline nature of polyindole. The FESEM images of polyindole revealed the formation of irregularly shaped particulate nature with size in the range of 0.2 to 6 micron. In FT-IR spectrum, the major peak at ∼ 3400 cm −1 indicates N-H stretching and at 1564−1624 cm −1 indicates C-C stretching of benzenoid ring of indole. The presence of peak at ∼ 3400 cm −1 indicates that the polymerization does not occur at nitrogen. The present protocol has certain advantages like recyclability, low loading of the catalyst, low-cost and efficient use of polyindole as a heterogeneous catalyst.

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Methyl‐substituted diindolylmethanes as inhibitors of estrogen‐induced growth of T47D cells and mammary tumors in rats

Cited by 71 publications

References 26 publications

Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer

Increased arylhydrocarbon receptor expression offers a potential therapeutic target for pancreatic cancer

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

Synthesis and characterization of Polyindole and its catalytic performance study as a heterogeneous catalyst

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