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Eun-Joo Jeon, Munkhtugs Davaatseren, Jin-Taek Hwang, Jae Ho Park, Haeng Jeon Hur, Ae Sin Lee, Mi Jeong Sung
In patients with inflammatory bowel disease (IBD), inflammation is induced and maintained by lymphangiogenesis and angiogenesis. 3,3'-Diindolylmethane (DIM) is a natural product formed in acidic conditions from indole-3-carbinol in cruciferous vegetables, and it is known for its chemotherapeutic activity. This study evaluated DIM's effects on angiogenesis, lymphangiogenesis, and inflammation in a mouse colitis model. Experimental colitis was induced in mice by administering 3% dextran sulfate sodium (DSS) via drinking water...
October 4, 2016: Journal of Agricultural and Food Chemistry
Barbara Licznerska, Wanda Baer-Dubowska
Indole-3-carbinol (I3C), a common phytochemical in cruciferous vegetables, and its condensation product, 3,3'-diindolylmethane (DIM) exert several biological activities on cellular and molecular levels, which contribute to their well-recognized chemoprevention potential. Initially, these compounds were classified as blocking agents that increase drug-metabolizing enzyme activity. Now it is widely accepted that I3C and DIM affect multiple signaling pathways and target molecules controlling cell division, apoptosis, or angiogenesis deregulated in cancer cells...
2016: Advances in Experimental Medicine and Biology
Mai M Abdelmageed, Reem N El-Naga, Ebtehal El-Demerdash, Mohamed M Elmazar
Sorafenib is the only chemotherapeutic agent currently approved for unresectable hepatocellular carcinoma (HCC). However, poor response rates have been widely reported. Indole-3-carbinol (I3C) is a potential chemopreventive phytochemical. The present study aimed to explore the potential chemomodulatory effects of I3C on sorafenib in HCC cells as well as the possible underlying mechanisms. I3C exhibited a greater cytotoxicity in HepG2 cells compared to Huh-7 cells (p < 0.0001). Moreover, the co-treatment of HepG2 cells with I3C and sorafenib was more effective (p = 0...
2016: Scientific Reports
Prasad R Dandawate, Dharmalingam Subramaniam, Roy A Jensen, Shrikant Anant
Breast cancer is the most common form of cancer diagnosed in women worldwide and the second leading cause of cancer-related deaths in the USA. Despite the development of newer diagnostic methods, selective as well as targeted chemotherapies and their combinations, surgery, hormonal therapy, radiotherapy, breast cancer recurrence, metastasis and drug resistance are still the major problems for breast cancer. Emerging evidence suggest the existence of cancer stem cells (CSCs), a population of cells with the capacity to self-renew, differentiate and be capable of initiating and sustaining tumor growth...
October 2016: Seminars in Cancer Biology
Mi-Ok Ko, Mi-Bo Kim, Sang-Bin Lim
We evaluated the potentials of ten isothiocyanates (ITCs) from cruciferous vegetables and radish root hydrolysate for inhibiting the growth of oral pathogens, with an emphasis on assessing any structure-function relationship. Structural differences in ITCs impacted their antimicrobial activities against oral pathogens differently. The indolyl ITC (indol-3-carbinol) was the most potent inhibitor of the growth of oral pathogens, followed by aromatic ITCs (benzyl ITC (BITC) and phenylethyl ITC (PEITC)) and aliphatic ITCs (erucin, iberin, and sulforaphene)...
September 2, 2016: Journal of Microbiology and Biotechnology
Arnetta Fletcher, Haiqiu Huang, Lu Yu, Quynhchi Pham, Liangli Yu, Thomas T Y Wang
Dietary supplements are widely used in the United States, but the safety issue remains unresolved. Immuno-deficient or immuno-compromised patients, estimated to exceed 10 million in the United States, are known to use dietary supplements. This population potentially may be susceptible to supplements' adverse effects. The cruciferous vegetable-derived indole-3-carbinol (I3C) is known for its possible protective effects against a number of chronic diseases and is commercially available as a dietary supplement...
August 31, 2016: Journal of Dietary Supplements
Francisco J Barba, Nooshin Nikmaram, Shahin Roohinejad, Anissa Khelfa, Zhenzhou Zhu, Mohamed Koubaa
Glucosinolates are a large group of plant secondary metabolites with nutritional effects, and are mainly found in cruciferous plants. After ingestion, glucosinolates could be partially absorbed in their intact form through the gastrointestinal mucosa. However, the largest fraction is metabolized in the gut lumen. When cruciferous are consumed without processing, myrosinase enzyme present in these plants hydrolyzes the glucosinolates in the proximal part of the gastrointestinal tract to various metabolites, such as isothiocyanates, nitriles, oxazolidine-2-thiones, and indole-3-carbinols...
2016: Frontiers in Nutrition
Lyndsey White, Shuhong Wu, Jing Ma, Bingliang Fang, Dong Liang
Oncrasins are a class of RNA polymerase II inhibitors. Oncrasin-72 is an indole-3 carbinol analog that has shown to inhibit growth and induce the cell death of various human cancer cell lines. Oncrasin-266, a prodrug of oncrasin-72, has been shown to have improved pharmacokinetic properties and safety than Oncrasin-72. With respect to the potential therapeutic advantages of this class of compounds, there is a need for further preclinical assessment for future clinical trials. The development of and validation of an analytical method is essential for the quantification of oncrasins in biological fluids for pharmacokinetic studies...
October 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Naomi Fujioka, Benjamin W Ransom, Steven G Carmella, Pramod Upadhyaya, Bruce R Lindgren, Astia Roper-Batker, Dorothy K Hatsukami, Vincent A Fritz, Charles Rohwer, Stephen S Hecht
Glucobrassicin in Brassica vegetables gives rise to indole-3-carbinol (I3C), a compound with potent anticancer effects in preclinical models. We previously showed that the urinary metabolite 3,3'-diindolylmethane (DIM) could discriminate between volunteers fed high and low doses of Brassica vegetables. However, the quantitative relationship between glucobrassicin exposure and urinary DIM level is unclear. We conducted a clinical trial to examine the hypotheses that a range of glucobrassicin exposure from Brassica vegetables is reflected in urinary DIM and that this effect plateaus...
October 2016: Cancer Prevention Research
Mei-Lin Wang, Shyh-Hsiang Lin, Yuan-Yu Hou, Yue-Hwa Chen
This study investigated the effects of indole-3-carbinol (I3C) on adipogenesis- and angiogenesis-associated factors in mature adipocytes. The cross-talk between mature adipocytes and endothelial cells (ECs) was also explored by cultivating ECs in a conditioned medium (CM) by using I3C-treated adipocytes. The results revealed that I3C significantly inhibited triglyceride accumulation in mature adipocytes in association with significantly increased expression of AhR and CYP1B1 proteins as well as slightly decreased nuclear factor erythroid-derived factor 2-related factor 2, hormone-sensitive lipase, and glycerol-3-phosphate dehydrogenase expression by mature adipocytes...
2016: International Journal of Molecular Sciences
Z Ashley, C Leader, I Sammut, F McDonald, R Walker, M Fronius
OBJECTIVE: Hypertension (HTN) impairs the regulation of blood flow leading to cardiovascular morbidity and mortality. A "new player" in blood-flow regulation is the endothelium Epithelial Sodium Channel (vascular ENaC). We hypothesise that dysfunction in HTN is due to changes in vascular ENaC activity. Aldosterone regulates renal ENaC and has a pivotal role in HTN and recently it has been suggested that aldosterone antagonism (spironolactone therapy) is beneficial beyond that predicted by the reduction in blood pressure...
September 2016: Journal of Hypertension
Bryant W Megna, Patrick R Carney, Manabu Nukaya, Pete Geiger, Gregory D Kennedy
BACKGROUND: Even with colonoscopy screening and preventive measures becoming more commonplace, colorectal cancer (CRC) remains the third leading cause of oncologic death in the United States as of 2014. Many chemotherapeutics exist for the treatment of colorectal cancer, though they often come with significant side effect profiles or narrow efficacy ranges in terms of patient profile. Dietary phytochemicals such as glucobrassicin and its metabolite indole-3-carbinol (I3C) have been implicated in tumor prevention in many preclinical models across a variety of gastrointestinal tumors and represent an intriguing new class of natural chemotherapeutics for CRC...
July 2016: Journal of Surgical Research
Carol J Díaz-Díaz, Sean M Ronnekleiv-Kelly, Manabu Nukaya, Peter G Geiger, Silvia Balbo, Romel Dator, Bryant W Megna, Patrick R Carney, Christopher A Bradfield, Gregory D Kennedy
OBJECTIVE: To determine the role of the aryl hydrocarbon receptor (AHR) in colitis-associated colorectal tumorigenesis. BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in United States. Chronic intestinal inflammation increases the risk for the development of CRC. We investigated the involvement of AHR, a ligand-activated transcriptional regulator, in colitis-associated colorectal tumorigenesis. METHODS: We used a mouse model of colitis-associated colorectal tumorigenesis that employs treatment with azoxymethane and dextran sodium sulfate...
September 2016: Annals of Surgery
Katharina Haas, Heike Weighardt, René Deenen, Karl Köhrer, Björn Clausen, Sonja Zahner, Petra Boukamp, Wilhelm Bloch, Jean Krutmann, Charlotte Esser
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in adaptive cell functions, and is highly active in the epidermis. AhR ligands can accelerate keratinocyte differentiation, but the precise role of AhR in the skin barrier is unknown. Our study showed that transepidermal water loss (TEWL), a parameter of skin barrier integrity, is high in AhR-deficient (AhR-KO) mice. Experiments with conditionally AhR-deficient mouse lines identified keratinocytes as the primary cell population responsible for high TEWL...
July 15, 2016: Journal of Investigative Dermatology
Šárka Jíchová, Libor Kopkan, Zuzana Husková, Šárka Doleželová, Jan Neckář, Petr Kujal, Zdenka Vernerová, Herbert J Kramer, Janusz Sadowski, Elzbieta Kompanowska-Jezierska, Rami N Reddy, John R Falck, John D Imig, Luděk Červenka
OBJECTIVE: We evaluated the therapeutic effectiveness of a new, orally active epoxyeicosatrienoic acid analog (EET-A) in rats with angiotensin II (ANG II)-dependent malignant hypertension. METHODS: Malignant hypertension was induced in Cyp1a1-Ren-2 transgenic rats by activation of the renin gene using indole-3-carbinol (I3C), a natural xenobiotic. EET-A treatment was started either simultaneously with I3C induction process (early treatment) or 10 days later during established hypertension (late treatment)...
October 2016: Journal of Hypertension
Reem N El-Naga, Yasmen F Mahran
Nephrotoxicity associated with the clinical use of the anticancer drug cisplatin is a limiting problem. Thus, searching for new protective measures is required. Indole-3-carbinol is a powerful anti-oxidant, anti-inflammatory and anti-tumor agent. The present study aimed to investigate the potential protective effect of indole-3-carbinol against cisplatin-induced acute nephrotoxicity in rats. Rats were pre-treated with 20 mg/kg indole-3-carbinol orally before giving cisplatin (7 mg/kg). Cisplatin-induced acute nephrotoxicity was demonstrated where relative kidney weight, BUN and serum creatinine were significantly increased...
2016: Scientific Reports
J Enríquez, R Velázquez-Cruz, A Parra-Torres, R Gutiérrez-Sagal, F Larrea
PURPOSE: To gain new insight into the roles of cruciferous vegetable-derived bioactive phytochemicals in bone cells, we investigated the effects of indole-3-carbinol (I3C) on cell proliferation and differentiation in estradiol (E2)-exposed calvarial osteoblasts that were obtained from neonatal rats. METHODS: Osteoblast activity was assessed by analyzing cellular DNA, cell-associated osteocalcin (OC) levels and alkaline phosphatase (AP) activity. We also examined [(3)H]-estrone (E1) metabolism and estrogen-agonistic and estrogen-antagonistic activities of 2-hydroxy (OH) E1 and 2-OHE2 and their capacity to displace [(3)H]-E2 at ER binding sites using competition studies...
October 2016: Journal of Endocrinological Investigation
Elisa Giambanelli, Ruud Verkerk, L Filippo D'Antuono, Teresa Oliviero
BACKGROUND: Kales are often a key ingredient of traditional foods, containing high amount of indolic glucosinolates (precursors of indole-3-carbinol and ascorbigen), carotenoids and phenolics. The present trend to associate traditional foods crops with health promoting properties, suggested to investigate the degradation kinetic of three Brassica oleracea landraces' phytochemicals, subjected to boiling, steaming and stir frying. RESULTS: Boiling determined substantial losses, due to leaching...
June 14, 2016: Journal of the Science of Food and Agriculture
Walker Julliard, Travis J De Wolfe, John H Fechner, Nasia Safdar, Rashmi Agni, Joshua D Mezrich
OBJECTIVE: To determine the therapeutic effects of dietary supplementation on Clostridium difficile infection (CDI). BACKGROUND: With limited treatment options, the rise of C. difficile-associated disease has spurred on the search for novel therapies. Recent data define a role for the aryl hydrocarbon receptor (AHR) and diet-derived AHR ligands in mucosal immunity. We investigated the efficacy of indole-3-carbinol (I3C), a dietary supplement, and AHR precursor ligand in a murine model of CDI...
June 8, 2016: Annals of Surgery
Pavel Babica, Lucie Čtveráčková, Zuzana Lenčešová, James E Trosko, Brad L Upham
Altered gap junctional intercellular communication (GJIC) has been associated with chemical carcinogenesis, where both chemical tumor promoters and chemopreventive agents (CPAs) are known to conversely modulate GJIC. The aim of this study was to investigate whether attenuation of chemically inhibited GJIC represents a common outcome induced by different CPAs, which could be effectively evaluated using in vitro methods. Rat liver epithelial cells WB-F344 were pretreated with a CPA for either 30 min or 24 h, and then exposed to GJIC-inhibiting concentration of a selected tumor promoter or environmental toxicant [12-O-tetradecanoylphorbol-13-acetate (TPA), lindane, fluoranthene, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), perfluorooctanoic acid (PFOA), or pentachlorophenol]...
July 2016: Nutrition and Cancer
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