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Dihydrolipoamide dehydrogenase regulates cystine deprivation-induced ferroptosis in head and neck cancer
We examined the role of dihydrolipoamide dehydrogenase (DLD) in ferroptosis induction in head and neck cancer (HNC). The effects of cystine deprivation or sulfasalazine treatment and of DLD gene silencing/overexpression were tested on HNC cell lines and mouse tumor xenograft models. These effects were analyzed with regard to cell death, lipid reactive oxygen species (ROS) and mitochondrial iron production, mitochondrial membrane potential, mRNA/protein expression, and α-ketoglutarate dehydrogenase (KGDH)/succinate/aconitase activities. Cystine deprivation induced ferroptosis via glutaminolysis. Cystine deprivation or impo...
Source: Redox Biology - January 8, 2020 Category: Biology Source Type: research

Inhibition of SGK1 confers vulnerability to redox dysregulation in cervical cancer
Publication date: Available online 20 May 2019Source: Redox BiologyAuthor(s): Min Wang, Yijue Xue, Lanlin Shen, Pan Qin, Xiaolin Sang, Zhiwei Tao, Jingyan Yi, Jia Wang, Pixu Liu, Hailing ChengAbstractCervical cancer has poor prognosis and patients are often diagnosed at advanced stages of the disease with limited treatment options. There is thus an urgent need for the discovery of new therapeutic strategies in cervical cancer. The activation of SGK1 has been linked to the development of various cancer types but little is known about the role of SGK1 in cervical cancer and its potential as a therapeutic target. Here we repo...
Source: Redox Biology - May 22, 2019 Category: Biology Source Type: research

Ku80 promotes melanoma growth and regulates antitumor effect of melatonin by targeting HIF1-α dependent PDK-1 signaling pathway
In this study, we screened a siRNA library targeting 6024 human genes and identified Ku80 as a potential therapeutic target in melanoma cells. Knockdown of Ku80 significantly suppressed melanoma cell proliferation and induced apoptosis, as well as enhanced the antitumor effect of melatonin in melanoma in vitro and in vivo. Overexpression of Ku80, however, promoted melanoma growth and increased the insensitivity of melanoma cells to melatonin. Mechanistically, we found that Ku80 bound to the PDK1 promoter and activated the transcription of PDK1. Moreover, we showed that the binding of Ku80 at the PDK-1 promoter was HIF1-α ...
Source: Redox Biology - April 22, 2019 Category: Biology Source Type: research

Specific Delivery of Delta-5-Desaturase siRNA via RNA Nanoparticles Supplemented with Dihomo-γ-Linolenic Acid for Colon Cancer Suppression
In this study, we employed RNA nanotechnology for specific delivery of D5D-siRNA to xenograft colon tumors using 3WJ RNA nanoparticles. When a targeting module, i.e., the EpCAM aptamer, was incorporated, the 3WJ pRNA nanoparticles were able specifically deliver D5D siRNA to human colon cancer HCA-7 cells both in vitro and in vivo, resulting in significant downregulation of D5D expression. Co-treatment with DGLA in combination with 3WJ-EpCAM-siRNA induced a higher DGLA/AA ratio and enhanced formation of 8-HOA at a threshold level, and in HCA-7 tumor-bearing mice, induced significant tumor suppression. We further confirmed t...
Source: Redox Biology - December 19, 2018 Category: Biology Source Type: research

Dihomo-γ-Linolenic Acid Inhibits Growth of Xenograft Tumors in Mice Bearing Human Pancreatic Cancer Cells (BxPC-3) Transfected with Delta-5-Desaturase shRNA
In this study, we have further investigated the anti-tumor effects of D5D-knockdown and the resulting intensified COX-2-catalyzed DGLA peroxidation in subcutaneous xenograft tumors. Four-week old female nude mice (Jackson Laboratory, J:Nu-007850) were injected with human pancreatic cancer cell line BxPC-3 or its D5D knockdown counterpart (via shRNA), followed by 4-week treatments of: vehicle control, DGLA supplementation (8 mg/mouse, twice a week), gemcitabine (30 mg/kg, twice a week), and a combination of DGLA and gemcitabine. In D5D-knockdown tumors, DGLA supplementation promoted 8-HOA formation to a threshold ...
Source: Redox Biology - October 17, 2018 Category: Biology Source Type: research

Nicotinamide nucleotide transhydrogenase-mediated redox homeostasis promotes tumor growth and metastasis in gastric cancer
In this study, we found that overexpression of nicotinamide nucleotide transhydrogenase (NNT) was associated with shorter overall and disease free survival in gastric cancer. The NNT is considered a key antioxidative enzyme based on its ability to regenerate NADPH from NADH. Knockdown of NNT caused significantly NADPH reduction, induced high levels of ROS and significant cell apoptosis under oxidative stress conditions such as glucose deprival and anoikis. In vivo experiments showed that NNT promoted tumor growth, lung metastasis and peritoneal dissemination of gastric cancer. Moreover, intratumoral injection of NNT siRNA ...
Source: Redox Biology - July 22, 2018 Category: Biology Source Type: research

The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading
Publication date: April 2018 Source:Redox Biology, Volume 14 Author(s): Anna Baulies, Joan Montero, Nuria Matías, Naroa Insausti, Oihana Terrones, Gorka Basañez, Carmen Vallejo, Laura Conde de La Rosa, Laura Martinez, David Robles, Albert Morales, Joaquin Abian, Montserrat Carrascal, Keigo Machida, Dinesh B.U. Kumar, Hidekazu Tsukamoto, Neil Kaplowitz, Carmen Garcia-Ruiz, José C. Fernández-Checa Cancer cells exhibit mitochondrial cholesterol (mt-cholesterol) accumulation, which contributes to cell death resistance by antagonizing mitochondrial outer membrane (MOM) permeabilization. Hepatocellular mt-cholesterol loadin...
Source: Redox Biology - September 28, 2017 Category: Biology Source Type: research

Expression of xCT and activity of system xc− are regulated by NRF2 in human breast cancer cells in response to oxidative stress
Publication date: Available online 18 March 2015 Source:Redox Biology Author(s): Eric Habib , Katja Linher-Melville , Han-Xin Lin , Gurmit Singh Cancer cells adapt to high levels of oxidative stress in order to survive and proliferate by activating key transcription factors. One such master regulator, the redox sensitive transcription factor NF E2 Related Factor 2 (NRF2), controls the expression of cellular defense genes including those encoding intracellular redox-balancing proteins involved in glutathione (GSH) synthesis. Under basal conditions, Kelch-like ECH-associated protein 1 (KEAP1) targets NRF2 for ubiquitinatio...
Source: Redox Biology - March 18, 2015 Category: Biology Source Type: research