Inhibition of proliferation of a colon cancer cell line by indole‐3‐carbinol

Frydoonfar, H. R.; McGrath, Daniel R; Spigelman, Allan D.

doi:10.1046/j.1463-1318.2002.00346.x

Cited by 47 publications

(31 citation statements)

References 7 publications

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“…I3C has been shown to suppress the proliferation of a wide variety of cells, including breast cancer cells, [9][10][11][12] colon cancer cells, [13][14][15] prostate cancer cells, 16,17 and endometrial cancer cells. 18 Katdare's group showed that I3C inhibits benzopyrene-induced proliferation of mammary epithelial cells.…”

Section: Antiproliferative Effects Of I3c Against Tumor Cellsmentioning

confidence: 99%

“…Using an in vitro system and a hepatic postmitochondrial fraction from mice that had been treated by gavage with I3C, they found that up to 90% of the covalent binding of BaP metabolites to macromolecules was eliminated, while AHH activity was unchanged. In experiments in vivo, treatment of mice by gavage with I3C before [ 14 C]BaP resulted in up to an 80% decrease in covalent binding of 14 C to DNA or protein with no concomitant decrease in hepatic AHH activity. These results suggest that I3C administered in vivo confers protection against the binding of BaP oxidation products to hepatic cellular macromolecules.…”

Section: I3c Prevents Carcinogen-dna Adduct Formationmentioning

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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Section: Antiproliferative Effects Of I3c Against Tumor Cellsmentioning

confidence: 99%

Section: I3c Prevents Carcinogen-dna Adduct Formationmentioning

confidence: 99%

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

2005

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“…The antiproliferative activity of some substituted indole and biindole derivatives against breast, colon, and lung cancer cells has been reported (Katdare et al, 1998;Chinni and Sarkar, 2002;Frydoonfar et al, 2002Frydoonfar et al, , 2003Hong et al, 2002;Howells et al, 2002;Zheng et al, 2002;Hudson et al, 2003;Nachshon-Kedmi et al, 2003;Rahman et al, 2003;Weng et al, 2008;Ji et al, 2013;Ali et al, 2014). The antiproliferative and cytotoxic activities of 2 against HeLa, C6, and HT29 cell lines were tested and documented for the first time in this study.…”

Section: Discussionmentioning

confidence: 67%

In vitro antiproliferative/cytotoxic activity of 2,3ʹ-biindole againstvarious cancer cell lines

Ökten

Erenler²,

Köprülü³

et al. 2015

Turk J Biol

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2,3'-Biindole (2) was synthesized via bromination of indole (1) with molecular bromine and underwent simultaneous dimerization. Antiproliferative and cytotoxic activity of 2 was investigated in vitro on C6 (rat brain tumor), HeLa (human cervix carcinoma), and HT29 (human colon carcinoma) cells lines by using BrdU cell proliferation ELISA and lactate dehydrogenase (LDH) assays. In contrast to 5-fluorouracil (5-FU), 2,3'-biindole (2) significantly inhibited proliferation of HeLa and HT29 cell lines. According to LDH assay, the cytotoxicity of compound 2 was low on HT29 cell lines and high on HeLa and C6 cell lines. Moreover, 2 did not cause any DNA laddering on the DNA of tested cells; therefore, it is suggested that the mechanism of action of this compound may not involve apoptosis. In addition, 2 inhibited relaxation of supercoiled plasmid DNA by topoisomerase activity. Results of the present study indicates that biindole (2) may have promising anticancer and antitopoisomerase potential with an unknown mechanism of action.

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“…[91] Indole-3-carbinol (I3C) and its derivatives ( Figure 20) are a class of compounds that have received considerable attention over the past 30 years. [92,93] I3C has been shown to be effective against a range of cancers including those of the breast, [94] colon [95][96][97] and prostate. [98][99][100] The activity of I3C is belived to be due to its intrinsic instability in acidic media, and the subsequent formation of its metabolites (Figure 20).…”

Section: Ros Producersmentioning

confidence: 99%

Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives

Sherer

Snape

2015

European Journal of Medicinal Chemistry

139

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HIGHLIGHTS• Brain cancer mortality rates are much higher than mortality rates for cancers of other sites. •Due to the blood brain barrier, many drugs that work on cancers of other sites do not work on brain cancers • Indoles, carbazoles and indolocarbazoles make good scaffolds for drugs to be built up around due to their rigidity, planarity and ease of synthesis. GRAPHICAL ABSTRACT ACRONYMS/INITIALISMSAML -Acute myeloid leukaemia CK2 -Casein kinase 2 CNS -Central nervous system PARP -Poly ADP ribose polymerase PDGF -Platelet-derived growth factor PKC -Protein kinase C ROS -Reactive oxygen species VEGF -Vascular endothelial growth factor ABSTRACT Tumours of the central nervous system are intrinsically more dangerous than tumours at other sites, and in particular, brain tumours are responsible for 3% of cancer deaths in the UK. Despite this, research into new therapies only receives 1% of national cancer research spend. The most common chemotherapies are temozolomide, procarbazine, carmustine, lomustine and vincristine, but because of the rapid development of chemoresistance, these drugs alone simply aren't sufficient for longterm treatment. Such poor prognosis of brain tumour patients prompted us to research new treatments for malignant glioma, and in doing so, it became apparent that aromatic heterocycles play an important part, especially the indole, carbazole and indolocarbazole scaffolds. This review highlights compounds in development for the treatment of tumours of the central nervous system which are structurally based on the indole, carbazole and indolocarbazole scaffolds, under the expectation that it will highlight new avenues for research for the development of new compounds to treat these devastating neoplasms.

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Inhibition of proliferation of a colon cancer cell line by indole‐3‐carbinol

Cited by 47 publications

References 7 publications

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

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

In vitro antiproliferative/cytotoxic activity of 2,3ʹ-biindole againstvarious cancer cell lines

Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives

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