Attenuation of Carcinogenesis and the Mechanism Underlying by the Influence of Indole-3-carbinol and Its Metabolite 3,3′-Diindolylmethane: A Therapeutic Marvel

Maruthanila, V L; Poornima, J.; Mirunalini, Sankaran

doi:10.1155/2014/832161

Cited by 51 publications

(54 citation statements)

References 52 publications

(88 reference statements)

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“…Moreover, our findings indicate that I3C may functions as a protector agent against AOM-induced DNA damage. To this regard, it is reported that I3C induces intestinal glutathione-S-transferase (GST), an enzyme involved in the detoxification of xenobiotics and in regulating antioxidant responses [32–34]. It is plausible, that I3C protective effect against DNA damage may be mediated by an increase in the detoxification of AOM, an alkylating agent that provokes DNA damage, resulting in antioxidant responses that confer protection within the colon.…”

Section: Discussionmentioning

confidence: 99%

“…I3C is a proagonist found in the Brassica family of vegetables. After ingestion, it undergoes condensation reactions within the acidic gastric environment resulting in several metabolites such as 3,3'-diindolylmethane (DIM) and indolo [3,2-b]carbazole (ICZ), both of which have high affinity for AHR [34]. Although the chemopreventive effect of I3C has been recognized before, this is the first study to establish that the I3C protective effect within the colon is dependent on AHR.…”

Section: Discussionmentioning

confidence: 99%

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The Aryl Hydrocarbon Receptor is a Repressor of Inflammation-associated Colorectal Tumorigenesis in Mouse

et al. 2016

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Objective To determine the role of the aryl hydrocarbon receptor (AHR) in colitis-associated colorectal tumorigenesis. Summary Background Data Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women in United States. Chronic intestinal inflammation increases the risk for the development of CRC. We questioned the involvement of AHR, a transcriptional regulator for intestinal innate immunity and inflammation, in the colitis-associated tumorigenesis. Methods We used a mouse model for chemically-induced colorectal tumorigenesis by treatment of azoxymethane (AOM) and sodium dextran sulfate (DSS). We examined the role of AHR using Ahr-deletion mouse model and I3C treatment. Tumor incidence, number and location were visually counted. Tumor multiplicities were evaluated and compared using GraphPad Prism software (version 6, LaJolla, CA). Results In Ahr null mice, the tumor incidence was 32% increased and the mean tumor number was approximately 3 time increased compared to WT mice (7 v 2.4, P<0.05). The tumor number was 92% decreased by treatment of I3C in WT mice, while the chemopreventive effect of I3C was not observed in Ahr null mice (P<0.05). Conclusions We found that the AHR may play a protective role in colitis-associated colorectal tumorigenesis. This work supports the application of AHR agonists such as I3C as a chemopreventive therapy for CRC in human patient.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor is a Repressor of Inflammation-associated Colorectal Tumorigenesis in Mouse

et al. 2016

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“…Medicinal plants are rich sources of important metabolites, which are potential sources of antioxidant, antimicrobial, anti-inflammatory, and anticancer activities (Hernandez et al, 2000; Polya, 2003; Maruthanila et al, 2014). The utilization of herbal medicine in treating infectious diseases have been practiced for 1000s of years and will continue to provide mankind with new remedies (Cragg and Newman, 2007).…”

Section: Introductionmentioning

confidence: 99%

In vitro and In vivo Antioxidant, Anti-hyperlipidemic Properties and Chemical Characterization of Centella asiatica (L.) Extract

et al. 2016

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The study aimed to identify the phenolic compounds present in Centella asiatica (L.) (C. asiatica) extract and evaluate the respective antioxidant potential as well as its cholesterol-lowering effects in the experimental animal model. Herein, the antioxidant potential of extracts was assessed by its free radical scavenging activity such as 2, 2-diphenyl -1- picrylhydrazyl as well as reducing capability. The anti-hyperlipidemic effects of C. asiatica extract (CAE) were evaluated in high cholesterol-fed (HCF) rats for 4 weeks, where different concentrations of extracts (0.25, 0.5, and 1 g/kg/day) were orally administrated daily. Lipid and antioxidant profiles, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and superoxide dismutase (SOD), together with the indices of hepatic functions were also examined. C. asiatica revealed excellent free radical scavenging activity as revealed by 2-2- diphenyl-1-picryl-hydrazyl (DPPH) assay, with the IC50 values (9.62 ± 0.88 μg/mL). Furthermore, C. asiatica extracts and fenofibrate remarkably lowered the level of TC, TG, LDL-C, and showed elevated levels of HDL-C, SOD. The histopathological observations further demonstrated clear differentiation and structural changes in liver of HCF and CAE treated group. Furthermore, gulonic acid, ferulic acid, kaempferol, chlorogenic acid, and asiatic acid were identified to be the major components which might be responsible for the antioxidant activity of the C. asiatica extract as evidenced from an ultra-high performance liquid chromatography–mass spectrometer. Taken together, these results signifies the excellent antioxidant and anti-hyperlipidemic properties of C. asiatica leaf extracts, which might be useful for the treatment of oxidative-stress related diseases such as hyperlipidemia.

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“…Both I3C and DIM have been reported to possess potent anticancer activity through its ability to regulate cancer cell cycle, induction of apoptosis and major oncogenic signaling pathways (144). In colon and pancreatic cancer cell lines, DIM treatment leads to induction in the expression of miR-146a thereby targeting EGFR, IRAK1 and NFkB mRNAs (145).…”

Section: Mirnas and Essential Nutritional Factorsmentioning

confidence: 99%

Manipulating MiRNA Expression: a Novel Approach for Colon Cancer Prevention and Chemotherapy

2015

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Small non-coding RNA has been implicated in the control of various cellular processes such as proliferation, apoptosis, and differentiation. About 50% of the miRNA genes are positioned in cancer-associated genomic regions. Several studies have shown that miRNA expression is deregulated in cancer and modulating their expression has reversed the cancer phenotype. Therefore, mechanisms to modulate microRNA (miRNA) activity have provided a novel opportunity for cancer prevention and therapy. In addition, a common cause for development of colorectal cancers is environmental and lifestyle factors. One such factor, diet has been shown to modulate miRNA expression in colorectal cancer patients. In this chapter, we will summarize the work demonstrating that miRNAs are novel promising drug targets for cancer chemoprevention and therapy. Improved delivery, increased stability and enhanced regulation of off-target effects will overcome the current challenges of this exciting approach in the field of cancer prevention and therapy.

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Attenuation of Carcinogenesis and the Mechanism Underlying by the Influence of Indole-3-carbinol and Its Metabolite 3,3′-Diindolylmethane: A Therapeutic Marvel

Cited by 51 publications

References 52 publications

The Aryl Hydrocarbon Receptor is a Repressor of Inflammation-associated Colorectal Tumorigenesis in Mouse

The Aryl Hydrocarbon Receptor is a Repressor of Inflammation-associated Colorectal Tumorigenesis in Mouse

In vitro and In vivo Antioxidant, Anti-hyperlipidemic Properties and Chemical Characterization of Centella asiatica (L.) Extract

Manipulating MiRNA Expression: a Novel Approach for Colon Cancer Prevention and Chemotherapy

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