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Jisung Kim, Siyoung Lee, Bo-Ryoung Choi, Hee Yang, Youjin Hwang, Jung Han Yoon Park, Frank M LaFerla, Jung-Soo Han, Ki Won Lee, Jiyoung Kim
SCOPE: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways. METHODS AND RESULTS: Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane...
October 13, 2016: Molecular Nutrition & Food Research
Shu-Hua Yang, Miao Long, Li-Hui Yu, Lin Li, Peng Li, Yi Zhang, Yang Guo, Feng Gao, Ming-Da Liu, Jian-Bin He
Sulforaphane (SFN) is a natural and highly effective antioxidant. Studies suggest that SFN protects cells and tissues against cadmium (Cd) toxicity. This study investigated the protective effect of SFN against oxidative damage in the testes of Kunming mice exposed to cadmium, and explored the possible molecular mechanisms involved. Cadmium greatly reduced the serum testosterone levels in mice, reduced sperm motility, total sperm count, and increased the sperm deformity rate. Cadmium also reduces superoxide dismutase (T-SOD) and glutathione (GSH) levels and increases malondialdehyde (MDA) concentrations...
October 11, 2016: International Journal of Molecular Sciences
Dushani L Palliyaguru, Dionysios V Chartoumpekis, Nobunao Wakabayashi, John J Skoko, Yoko Yagishita, Shivendra V Singh, Thomas W Kensler
Small molecules of plant origin offer presumptively safe opportunities to prevent carcinogenesis, mutagenesis and other forms of toxicity in humans. However, the mechanisms of action of such plant-based agents remain largely unknown. In recent years the stress responsive transcription factor Nrf2 has been validated as a target for disease chemoprevention. Withania somnifera (WS) is a herb used in Ayurveda (an ancient form of medicine in South Asia). In the recent past, withanolides isolated from WS, such as Withaferin A (WA) have been demonstrated to be preventive and therapeutic against multiple diseases in experimental models...
October 4, 2016: Free Radical Biology & Medicine
Tomasz Cierpiał, Jerzy Łuczak, Małgorzata Kwiatkowska, Piotr Kiełbasiński, Lidia Mielczarek, Katarzyna Wiktorska, Zdzisław Chilmonczyk, Małgorzata Milczarek, Katarzyna Karwowska
A series of previously unknown sulforaphane analogues with organofluorine substituents bonded to the sulfinyl sulfur atom, an isoselenocyanate moiety in place of the isothiocyanate group, the central sulfur atom in various oxidation states, and different numbers of methylene groups in the central alkyl chain were synthesized and fully characterized. All new compounds were tested for their biological properties in vitro and demonstrated much higher anticancer activity against two breast cancer cell lines than that shown by native sulforaphane; at the same time, the compounds were less toxic for normal cells...
October 7, 2016: ChemMedChem
I S Haslam, L Jadkauskaite, Imre Lőrinc Szabó, S Staege, J Hesebeck-Brinckmann, G Jenkins, R Bhogal, F L Lim, N Farjo, B Farjo, T Bíró, M Schäfer, R Paus
The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of Nrf2, the "master regulator" of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ, human scalp hair follicles (HFs)...
October 1, 2016: Journal of Investigative Dermatology
Xudong Zhao, Liting Wen, Min Dong, Xiaojie Lu
Nrf2-ARE pathway reportedly plays a protective role in several central nervous system diseases. No study has explored the role of the Nrf2-ARE pathway in cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the present study was to investigate the activation of the cerebral vascular Nrf2-ARE pathway and to determine the potential role of this pathway in the development of CVS following SAH. We investigated whether the administration of sulforaphane (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway activity, proinflammatory cytokine expression, and clinical behaviour in a rat model of SAH...
September 27, 2016: Brain Research
Junhui Shao, Jiang Huang, Yana Guo, Lijuan Li, Xueqin Liu, Xiaoxuan Chen, Junfa Yuan
Generation of reactive oxygen species (ROS) and failure to maintain an appropriate redox balance contribute to viral pathogenesis. Nuclear factor E2-related factor 2 (Nrf2) is an important transcription factor that plays a pivotal role in maintaining intracellular homoeostasis and coping with invasive pathogens by coordinately activating a series of cytoprotective genes. Previous studies indicated that the transcription and expression levels of Nrf2 were up-regulated in SVCV-infected EPC cells with the unknown mechanism(s)...
September 28, 2016: Fish & Shellfish Immunology
Qin Yang, Maren J Pröll, Dessie Salilew-Wondim, Rui Zhang, Dawit Tesfaye, Huitao Fan, Mehmet U Cinar, Christine Große-Brinkhaus, Ernst Tholen, Mohammad A Islam, Michael Hölker, Karl Schellander, Muhammad J Uddin, Christiane Neuhoff
Pulmonary alveolar macrophages (AMs) are important in defense against bacterial lung inflammation. Cluster of differentiation 14 (CD14) is involved in recognizing bacterial lipopolysaccharide (LPS) through MyD88-dependent and TRIF pathways of innate immunity. Sulforaphane (SFN) shows anti-inflammatory activity and suppresses DNA methylation. To identify CD14 epigenetic changes by SFN in the LPS-induced TRIF pathway, an AMs model was investigated in vitro CD14 gene expression was induced by 5 µg/ml LPS at the time point of 12 h and suppressed by 5 µM SFN...
September 29, 2016: Innate Immunity
Young S Cho, Chan H Kim, Tae S Ha, Hee Y Ahn
Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) play key roles in the initiation of vascular inflammation. In this study, we explored whether sulforaphane, a dietary phytochemical, can inhibit the expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS), and the mechanisms involved. Sulforaphane prevented the LPS-mediated increase in ICAM-1 and VCAM-1 expression, (P < 0.01) in HUVEC. Sulforaphane also prevented the LPS-mediated increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) (P < 0...
November 18, 2015: Canadian Journal of Physiology and Pharmacology
Yung-Ju Chen, Angela D Myracle, Matthew A Wallig, Elizabeth H Jeffery
Western-style high fat, high sugar diets are associated with non-alcoholic fatty liver disease (NAFLD) and increased liver cancer risk. Sulforaphane from broccoli may protect against these. Previously we initiated broccoli feeding to mice prior to exposure to the hepatocarcinogen diethylnitrosamine (DEN), and saw protection against NAFLD and liver cancer. Here we administered DEN to unweaned mice, initiating broccoli feeding two weeks later, to determine if broccoli protects against cancer progression. Specifically, male 15-day-old C57BL/6J mice were given DEN and placed on a Western or Western+10%Broccoli diet from the age of 4 weeks through 7 months...
June 2016: Journal of Functional Foods
Silvio Holzner, Daniel Senfter, Serena Stadler, Anna Staribacher, Chi Huu Nguyen, Anna Gaggl, Silvana Geleff, Nicole Huttary, Sigurd Krieger, Walter Jäger, Helmut Dolznig, Robert M Mader, Georg Krupitza
Since cancer cells, when grown as spheroids, display drug sensitivity and radiation resistance patterns such as seen in vivo we recently established a three‑dimensional (3D) in vitro model recapitulating colorectal cancer (CRC)-triggered lymphatic endothelial cell (LEC)‑barrier breaching to study mechanisms of intra‑/extravasation. CRC metastasizes not only through lymphatics but also through blood vessels and here we extend the 3D model to the interaction of blood endothelial cells (BECs) with naïve and 5‑fluorouracil (5‑FU)‑resistant CRC CCL227 cells...
September 20, 2016: Oncology Reports
V Calabrese, J Giordano, M Ruggieri, D Berritta, A Trovato, M L Ontario, R Bianchini, E J Calabrese
In the United States, 1.1-1.5% of children have been diagnosed with autism spectrum disorders (ASD), corresponding to a 30% increase in incidence and prevalence. Social and communication impairments are the main signs and symptoms of ASD, and currently available medications have been ineffective in reducing these core deficits. Observational studies have indicated that children with ASD tend to show improved cognition and behavior after febrile illness, which is associated with alteration of metabolic pathways, leading to cellular stress responses and increased expression of heat shock proteins (Hsps)...
December 2016: Journal of Neuroscience Research
Katarzyna Lubelska, Katarzyna Wiktorska, Lidia Mielczarek, Małgorzata Milczarek, Ilona Zbroińska-Bregisz, Zdzisław Chilmonczyk
Sulforaphane (SFN), a naturally occurring chemopreventive and anticancer agent, is a nuclear factor, erythroid 2-like 2 (NFE2L2/Nrf2) inducer. Nrf2 plays a critical role in coordinating the cell defense system by initiating the transcription of cytoprotective genes, including detoxification enzymes such as NAD(P)H quinone dehydrogenase 1 (NQO1) and transport proteins such as ATP-binding cassette, subfamily C (CFTR/MRP). Recently, the essential role of Nrf2 in tumor development and progression and in the development of multidrug resistance in cancer cells has been highlighted...
September 16, 2016: Nutrition and Cancer
Sarah Maria Johler, Jörg Fuchs, Guido Seitz, Sorin Armeanu-Ebinger
Macrophage migration inhibitory factor (MIF) is known to be involved in oncogenic transformation, tumour progression, and immunosuppression and is overexpressed in many solid tumours, including paediatric rhabdomyosarcoma (RMS). We investigated the function of MIF in RMS during treatment with cytotoxic drugs. RMS cell lines were analysed by flow cytometry, immunofluorescence staining, and ELISA. We demonstrated the overexpression of MIF in RMS cells and the enhanced expression and secretion after treatment with cytotoxic agents...
September 15, 2016: Cancer Immunology, Immunotherapy: CII
Kuo-Ching Liu, Ting-Ying Shih, Chao-Lin Kuo, Yi-Shih Ma, Jiun-Long Yang, Ping-Ping Wu, Yi-Ping Huang, Kuang-Chi Lai, Jing-Gung Chung
Sulforaphane (SFN), an isothiocyanate, exists exclusively in cruciferous vegetables, and has been shown to possess potent antitumor and chemopreventive activity. However, there is no available information that shows SFN affecting human colon cancer HCT 116 cells. In the present study, we found that SFN induced cell morphological changes, which were photographed by contrast-phase microscopy, and decreased viability. SFN also induced G2/M phase arrest and cell apoptosis in HCT 116 cells, which were measured with flow cytometric assays...
2016: American Journal of Chinese Medicine
Ya-Min Cheng, Ching-Chou Tsai, Yi-Chiang Hsu
Globally, cervical cancer is the most common malignancy affecting women. The main treatment methods for this type of cancer include conization or hysterectomy procedures. Sulforaphane (SFN) is a natural, compound-based drug derived from dietary isothiocyanates which has previously been shown to possess potent anti-tumor and chemopreventive effects against several types of cancer. The present study investigated the effects of SFN on anti-proliferation and G₂/M phase cell cycle arrest in cervical cancer cell lines (Cx, CxWJ, and HeLa)...
2016: International Journal of Molecular Sciences
Jamie L Lim, Susanne M A van der Pol, Wia Baron, Joe M McCord, Helga E de Vries, Jack van Horssen
Oligodendrocyte damage and loss are key features of multiple sclerosis (MS) pathology. Oligodendrocytes appear to be particularly vulnerable to reactive oxygen species (ROS) and cytokines, such as tumor necrosis factor-α (TNF), which induce cell death and prevent the differentiation of oligodendrocyte progenitor cells (OPCs). Here, we investigated the efficacy of sulforaphane (SFN), monomethyl fumarate (MMF) and Protandim to induce Nrf2-regulated antioxidant enzyme expression, and protect oligodendrocytes against ROS-induced cell death and ROS-and TNF-mediated inhibition of OPC differentiation...
September 7, 2016: Antioxidants (Basel, Switzerland)
Karamatullah Danyal, Willem de Jong, Edmund O'Brien, Robert Alan Bauer, David Earl Heppner, Andrew Little, Milena Hristova, Aida Habibovic, Albert van der Vliet
Acrolein is a major thiol-reactive component of cigarette smoke (CS) that is thought to contribute to increased asthma incidence associated with smoking. Here, we explored the effects of acute acrolein exposure on innate airway responses to two common airborne allergens, house dust mite and Alternaria alternata, and observed that acrolein exposure of C57BL/6 mice (5 ppm, 4 hrs) dramatically inhibited innate airway responses to subsequent allergen challenge, demonstrated by attenuated release of the epithelial-derived cytokines IL-33, IL-25, and IL-1α...
September 9, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Teng-Fei Yin, Min Wang, Ying Qing, Ying-Min Lin, Dong Wu
Colorectal cancer (CRC) is a type of cancer with high morbidity and mortality rates worldwide and has become a global health problem. The conventional radiotherapy and chemotherapy regimen for CRC not only has a low cure rate but also causes side effects. Many studies have shown that adequate intake of fruits and vegetables in the diet may have a protective effect on CRC occurrence, possibly due to the special biological protective effect of the phytochemicals in these foods. Numerous in vitro and in vivo studies have demonstrated that phytochemicals play strong antioxidant, anti-inflammatory and anti-cancer roles by regulating specific signaling pathways and molecular markers to inhibit the occurrence and development of CRC...
August 21, 2016: World Journal of Gastroenterology: WJG
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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