Disulfiram causes selective hypoxic cancer cell toxicity and radio-chemo-sensitization via redox cycling of copper.

Disulfiram causes selective hypoxic cancer cell toxicity and radio-chemo-sensitization via redox cycling of copper. Free Radic Biol Med. 2020 Feb 04;: Authors: Falls-Hubert KC, Butler AL, Gui K, Anderson M, Li M, Stolwijk JM, Rodman SN, Solst SR, Tomanek-Chalkley A, Searby CC, Sheffield VC, Sandfort V, Schmidt H, McCormick M, Wels BR, Allen BG, Buettner GR, Schultz MK, Spitz DR Abstract Therapies for lung cancer patients initially illicit desirable responses, but the presence of hypoxia and drug resistant cells within tumors ultimately lead to treatment failure. Disulfiram (DSF) is an FDA approved, copper chelating agent that can target oxidative metabolic frailties in cancer vs. normal cells and be repurposed as an adjuvant to cancer therapy. Clonogenic survival assays showed that DSF (50-150 nM) combined with physiological levels of Cu (15 μM CuSO4) was selectively toxic to H292 NSCLC cells versus normal human bronchial epithelial cells (HBEC). Furthermore, cancer cell toxicity was exacerbated at 1% O2, relative to 4 or 21% O2. This selective toxicity of DSF/Cu was associated with differential Cu ionophore capabilities. DSF/Cu treatment caused a>20-fold increase in cellular Cu in NSCLCs, with nearly two-fold higher Cu present in NSCLCs vs. HBECs and in cancer cells at 1% O2vs. 21% O2. DSF toxicity was shown to be dependent on the retention of Cu as well as oxidative stress mechanisms, including the production of superoxide, peroxide, lipid pe...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research

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This study reports herein that gemcitabine synergizes with RASSF1A, silencing to increase the IAP-2 expression, which in turn not only interferes with cell proliferation but also promotes cell migration. This contributes to the aggressive behavior of RASSF1A-depleted cells, as confirmed by a combined knockdown of IAP-2 and RASSF1A. Conversely, paclitaxel does not increase the IAP-2 expression but limits the invasiveness of RASSF1A-depleted cells, presumably by rescuing microtubule stabilization. Overall, these data provide a functional insight that supports the prognostic value of RASSF1 gene methylation on survival of ear...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSIONS lncRNA TSLNC8 remarkably inhibited the proliferation and migration and accelerated apoptosis of lung cancer cells by targeting the IL-6/STAT3/HIF-1alpha signaling pathway. TSLNC8 may be a potential therapeutic target for the diagnosis and treatment of NSCLC. PMID: 31601776 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
In this study, we further examined this process in vivo by using heterozygous PARG knockout mice (PARG+/−). Wild-type and PARG+/− mice were individually treated with 0 or 10 μg/m3 BaP for 90 or 180 days by dynamic inhalation exposure. Pathological analysis of lung tissues showed that, with extended exposure time, carcinogenesis and injury in the lungs of WT mice was progressively worse; however, the injury was minimal and carcinogenesis was not detected in the lungs of PARG+/− mice. These results indicate that PARG gene silencing protects mice against lung cancer induced by BaP inhalation exposure. Fur...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Acetylcholine receptors (AChRs), including nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), are highly expressed in bronchial epithelial cells. We used The Cancer Genome Atlas (TCGA) data set to evaluate the expression pattern and prognostic value of the AChR gene family in non-small cell lung cancer (NSCLC). The mined data was validated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The survival analysis of TCGA data set showed that only CHRNA7 in the AChR gene family affected prognosis in both lung adenocarcinoma and lung squamous...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
Mark E. Gray1,2*, James Meehan2,3, Paul Sullivan4, Jamie R. K. Marland4, Stephen N. Greenhalgh1, Rachael Gregson1, Richard Eddie Clutton1, Carol Ward2, Chris Cousens5, David J. Griffiths5, Alan Murray4 and David Argyle1 1The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom 2Cancer Research UK Edinburgh Centre and Division of Pathology Laboratories, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom 3School of Engineering and Physical Sciences, Institute of Sensors, Signals and Systems, Heriot-Watt Univer...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
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Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
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Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
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