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indole-3-carbinol

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https://www.readbyqxmd.com/read/28418923/osu-a9-inhibits-pancreatic-cancer-cell-lines-by-modulating-p38-jak-stat3-signaling
#1
Wan-Chi Tsai, Li-Yuan Bai, Yi-Jin Chen, Po-Chen Chu, Ya-Wen Hsu, Aaron M Sargeant, Jing-Ru Weng
Pancreatic cancer is an aggressive malignancy that is the fourth leading cause of death worldwide. Since there is a dire need for novel and effective therapies to improve the poor survival rates of advanced pancreatic cancer patients, we analyzed the antitumor effects of OSU-A9, an indole-3-carbinol derivative, on pancreatic cancer cell lines in vitro and in vivo. OSU-A9 exhibited a stronger antitumor effect than gemcitabine on two pancreatic cancer cell lines, including gemcitabine-resistant PANC-1 cells. OSU-A9 treatment induced apoptosis, the down-regulation of Akt phosphorylation, up-regulation of p38 phosphorylation and decreased phosphorylation of JAK and STAT3...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396636/enhancing-drug-efficacy-and-therapeutic-index-through-cheminformatics-based-selection-of-small-molecule-binary-weapons-that-improve-transporter-mediated-targeting-a-cytotoxicity-system-based-on-gemcitabine
#2
Justine M Grixti, Steve O'Hagan, Philip J Day, Douglas B Kell
The transport of drug molecules is mainly determined by the distribution of influx and efflux transporters for which they are substrates. To enable tissue targeting, we sought to develop the idea that we might affect the transporter-mediated disposition of small-molecule drugs via the addition of a second small molecule that of itself had no inhibitory pharmacological effect but that influenced the expression of transporters for the primary drug. We refer to this as a "binary weapon" strategy. The experimental system tested the ability of a molecule that on its own had no cytotoxic effect to increase the toxicity of the nucleoside analog gemcitabine to Panc1 pancreatic cancer cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28395284/indole-3-carbinol-induces-apoptosis-of-hepatic-stellate-cells-through-k63-de-ubiquitination-of-rip1-in-rats
#3
Bin Li, Meng Cong, Yanan Zhu, Ying Xiong, Wenyi Jin, Yang Wan, Yunjiao Zhou, Ying Ao, Hui Wang
BACKGROUND/AIMS: The apoptosis of activated hepatic stellate cells (HSCs) is the central event in the reversal of liver fibrosis. K63 de-ubiquitinated receptor-interacting protein (RIP)1 promotes apoptosis in tumor necrosis factor (TNF)-α signaling pathway. In the previous study, we have proved that indole-3-carbinol (I3C) could reverse different models of liver fibrosis in rats, but the mechanism is still unclear. Thus, the present research aimed to demonstrate the induction of I3C on apoptosis of HSCs and the underlying molecular mechanism...
March 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28382865/multitargeted-molecular-docking-study-of-natural-derived-alkaloids-on-breast-cancer-pathway-components
#4
Ramit Singla, Vikas Jaitak
BACKGROUND: Targeting of multiple sites is a pharmacologically, pharmacokinetic and dynamically more acceptable approach for complex diseases such as BC. It is recommended that the women who are at high risk of developing BC might be given foods enhanced by indole alkaloids from vegetables like cabbage and broccoli. Administration of indole-3-carbinol is associated with decreased incidence of hormone-responsive BC (HRBC) which is implicated due to the induction of cytochrome P450 and glutathione-S-transferase which metabolizes chemical mutagens and by altering estrogen metabolism...
April 6, 2017: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/28357125/in-vitro-analysis-of-factors-influencing-cyp1a2-expression-as-potential-determinants-of-interindividual-variation
#5
ChengHui Xie, Marta Pogribna, Beverly Word, Lascelles Lyn-Cook, Beverly D Lyn-Cook, George J Hammons
Individual differences in drug metabolism contribute to interindividual variation that characterizes responses to drugs and risk in exposure to foreign chemicals. Large individual differences are found in expression levels of CYP1A2, a major drug-metabolizing enzyme. Underlying causes for this variation are not well understood. Several factors, including tobacco smoking, consumption of cruciferous vegetables, and sex, have been associated with modulating CYP1A2 expression. To understand factors regulating expression of CYP1A2 in establishing a causal relationship, this study examined effects of cigarette smoke condensate (CSC), indole-3-carbinol (I3C), and 17β-estradiol (estradiol) on CYP1A2 expression in in vitro systems using human liver and lung cells...
April 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28316274/co-treatment-with-indole-3-carbinol-and-resveratrol-modify-porcine-cyp1a-and-cyp3a-activities-and-expression
#6
Galia Zamaratskaia, Rebekka Thøgersen, Marjeta Čandek-Potokar, Martin Krøyer Rasmussen
1. Humans and animals are commonly exposed to indole-3-carbinol (I3C) and resveratrol (RES) via food or beverages. Moreover, these compounds have been demonstrated to potentially cause food-drug interactions. However, information about their combined effects is limited. Therefore, we investigated the effects of I3C and RES, both as single compounds and in combination, on cytochrome P450 1A and 3A activity and gene expression. 2. Using porcine microsomes, we demonstrated that RES caused non-competitive inhibition of CYP1A activity and un-competitive inhibition of CYP3A activity...
March 19, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28267258/normal-human-immune-cells-are-sensitive-to-telomerase-inhibition-by-brassica-derived-3-3-diindolylmethane-partly-mediated-via-er%C3%AE-%C3%AE-ap1-signalling
#7
Corinna Herz, Hoai Thi Thu Tran, Steffen Landerer, Johanna Gaus, Nina Schlotz, Lia Lehr, Wolfgang R Schäfer, Oliver Treeck, Grace Akinyi Odongo, Ivan Skatchov, Evelyn Lamy
SCOPE: Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) from Brassica plants are regarded as promising anticancer phytochemicals. The enzyme telomerase is a very attractive target for cancer therapeutics; in normal cells such as lymphocytes, it plays a decisive role for cell maintenance. The effect of I3C and DIM on telomerase in normal human immune cells (PBMC) was studied compared to leukaemia cells (HL-60). Signalling of telomerase regulation via estrogen receptor (ER) was addressed...
March 7, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28256372/preliminary-sar-on-indole-3-carbinol-and-related-fragments-reveals-a-novel-anticancer-lead-compound-against-resistant-glioblastoma-cells
#8
Christopher Sherer, Ibrahim Tolaymat, Farzana Rowther, Tracy Warr, Timothy J Snape
The prognosis for glioblastoma patients is, at best, poor, with the median time of survival after diagnosis measured in months. As such, there is much need for the rapid development of potent and novel treatments. Herein, we report our preliminary findings on the SAR of a series of indole-3-carbinol and related fragments and reveal a potent lead with low micromolar activity against a particularly resistant glioblastoma cell culture, providing a new platform for future development of a new therapy in this area...
April 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28254296/enhanced-photostability-radical-scavenging-and-antitumor-activity-of-indole-3-carbinol-loaded-rose-hip-oil-nanocapsules
#9
Mailine Gehrcke, Laura Minussi Giuliani, Luana Mota Ferreira, Allanna Valentini Barbieri, Marcel Henrique Marcondes Sari, Elita Ferreira da Silveira, Juliana Hofstatter Azambuja, Cristina Wayne Nogueira, Elizandra Braganhol, Letícia Cruz
This study aimed to develop poly(ε-caprolactone) nanocapsules loaded with indole-3-cabinol (I3C) using rose hip oil (RHO) or medium chain triglycerides (MCT) as oil core. In vitro radical scavenging activity (DPPH method), hemolysis, and antitumor effects on breast (MCF-7) and glioma (C6) cells were conducted. Preformulation evaluations revealed that RHO is suitable to prepare the nanocapsules considering the log P determination and dissolution/swelling experiments of polymer films. The nanocapsules were prepared and presented adequate physicochemical characteristics as mean size around 250nm, polydispersity index values <0...
May 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28137215/targeting-cancer-stem-cells-for-chemoprevention-of-pancreatic-cancer
#10
Dharmalingam Subramaniam, Gaurav Kaushik, Prasad Dandawate, Shrikant Anant
Pancreatic ductal adenocarcinoma is one of the deadliest cancers worldwide and the fourth leading cause of cancer-related deaths in United States. Regardless of the advances in molecular pathogenesis and consequential efforts to suppress the disease, this cancer remains a major health problem in United States. By 2030, the projection is that pancreatic cancer will be climb up to be the second leading cause of cancer-related deaths in the United States. Pancreatic cancer is a rapidly invasive and highly metastatic cancer, and does not respond to standard therapies...
January 26, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28117016/food-as-pharma-the-case-of-glucosinolates
#11
Edoardo Capuano, Matthijs Dekker, Ruud Verkerk, Teresa Oliviero
BACKGROUND: Glucosinolates (GLSs) are dietary plant secondary metabolites occurring in the order Brassicales with potential health effects, in particular as anti-carcinogenic compounds. GLSs are converted into a variety of breakdown products (BPs) upon plant tissue damage and by the gut microbiota. GLS biological activity is related to BPs rather than to GLSs themselves. METHODS: we have reviewed the most recent scientific literature on the metabolic fate and the biological effect of GLSs with particular emphasis on the epidemiological evidence for health effect and evidence from clinical trials...
January 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27979631/indole-3-carbinol-i3c-analogues-are-potent-small-molecule-inhibitors-of-nedd4-1-ubiquitin-ligase-activity-that-disrupt-proliferation-of-human-melanoma-cells
#12
Jeanne G Quirit, Sergey N Lavrenov, Kevin Poindexter, Janice Xu, Christine Kyauk, Kathleen A Durkin, Ida Aronchik, Thomas Tomasiak, Yaroslav A Solomatin, Maria N Preobrazhenskaya, Gary L Firestone
The HECT domain-containing E3 ubiquitin ligase NEDD4-1 (Neural precursor cell Expressed Developmentally Down regulated gene 4-1) is frequently overexpressed in human cancers and displays oncogenic-like properties through the ubiquitin-dependent regulation of multiple protein substrates. However, little is known about small molecule enzymatic inhibitors of HECT domain-containing ubiquitin ligases. We now demonstrate that indole-3-carbinol (I3C), a natural anti-cancer phytochemical derived from cruciferous vegetables such as cabbage and broccoli, represents a new chemical scaffold of small molecule enzymatic inhibitors of NEDD4-1...
March 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27916218/fenofibrate-attenuates-malignant-hypertension-by-suppression-of-the-renin-angiotensin-system-a-study-in-cyp1a1-ren-2-transgenic-rats
#13
Šárka Jíchová, Šárka Doleželová, Libor Kopkan, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Luděk Červenka
BACKGROUND: Malignant hypertension is a life-threatening condition, and its pathophysiology is still poorly understood. The present study was designed to evaluate the role of interaction of the renin-angiotensin system with 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway, in the pathophysiology of angiotensin II (ANG II)-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. METHODS: Malignant hypertension was induced by 12 days׳ dietary administration of 0...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27823732/cancer-chemoprevention-by-dietary-phytochemicals-epidemiological-evidence
#14
REVIEW
Raúl Baena Ruiz, Pedro Salinas Hernández
BACKGROUND: In recent years, natural compounds called "phytochemicals", which are present in fruits, vegetables, and plants, have received special attention due to their potential to interfere with tumour formation and development. Many of these phytochemicals are being used in chemoprevention strategies. However, the scientific evidence regarding the modification of cancer risk continues to be debated. OBJECTIVE: The aim of this paper is to review the current scientific evidence and the most relevant epidemiological studies regarding the consumption or use of phytochemicals and their effects on the incidence of cancer...
December 2016: Maturitas
https://www.readbyqxmd.com/read/27791173/prolactin-alters-blood-pressure-by-modulating-the-activity-of-endothelial-nitric-oxide-synthase
#15
Albert S Chang, Ruriko Grant, Hirofumi Tomita, Hyung-Suk Kim, Oliver Smithies, Masao Kakoki
Increased levels of a cleaved form of prolactin (molecular weight 16 kDa) have been associated with preeclampsia. To study the effects of prolactin on blood pressure (BP), we generated male mice with a single-copy transgene (Tg; inserted into the hypoxanthine-guanine phosphoribosyltransferase locus) that enables inducible hepatic production of prolactin and its cleavage product. The Tg is driven by the indole-3-carbinol (I3C)-inducible rat cytochrome P450 1A1 promoter. When the Tg mice were fed normal chow (NC), plasma prolactin concentrations were comparable to those in female WT mice in the last third of pregnancy, and BP was lower than in WT mice (∼95 mm Hg vs...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27783115/aryl-hydrocarbon-receptor-signaling-modifies-toll-like-receptor-regulated-responses-in-human-dendritic-cells
#16
Sarah Kado, W L William Chang, Aimy Nguyen Chi, Monika Wolny, David M Shepherd, Christoph F A Vogel
Currently, it is not well understood how ligands of the aryl hydrocarbon receptor (AhR) modify inflammatory responses triggered by Toll-like receptor (TLR) agonists in human dendritic cells (DCs). Here, we show that AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the tryptophan derivatives 6-formylindolo[3,2-b] carbazole (FICZ), kynurenine (kyn), and the natural dietary compound indole-3-carbinol (I3C) differentially modify cytokine expression in human monocyte-derived DCs (MoDCs). The results show that TLR-activated MoDCs express higher levels of AhR and are more sensitive toward the effects of AhR ligands...
May 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/27700072/effect-of-oral-administration-of-3-3-diindolylmethane-on-dextran-sodium-sulfate-induced-acute-colitis-in-mice
#17
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
https://www.readbyqxmd.com/read/27671815/indole-3-carbinol-and-its-role-in-chronic-diseases
#18
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
https://www.readbyqxmd.com/read/27612096/indole-3-carbinol-enhances-sorafenib-cytotoxicity-in-hepatocellular-carcinoma-cells-a-mechanistic-study
#19
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...
September 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27609747/targeting-cancer-stem-cells-and-signaling-pathways-by-phytochemicals-novel-approach-for-breast-cancer-therapy
#20
REVIEW
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
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