Regulation of NADPH oxidase NOX4 by delta iodolactone (IL-δ) in thyroid cancer cells

Thomasz, Lisa; Oglio, Romina; Salvarredi, Leonardo; Perona, Marina; Rossich, Luciano; Copelli, Silvia; Pisarev, Mario A.; Juvenal, Guillermo

doi:10.1016/j.mce.2017.10.004

Cited by 10 publications

(4 citation statements)

References 41 publications

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“…Our results are in the line with other findings, which report a significant increase in oxidative stress parameters in the cancer type of the cell line after exposition to the several groups of lactones [53]. Thomasz et al also showed that IL-δ increased ROS production by about 30% as well as increased lipid peroxidation levels about 19% in the HT-29 colon cancer cells.…”

Section: Oxidative Stress Markers Analysissupporting

confidence: 93%

Antiproliferative, Antimicrobial and Antiviral Activity of β-Aryl-δ-iodo-γ-lactones, Their Effect on Cellular Oxidative Stress Markers and Biological Membranes

et al. 2020

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The aim of this work was the examination of biological activity of three selected racemic cis-β-aryl-δ-iodo-γ-lactones. Tested iodolactones differed in the structure of the aromatic fragment of molecule, bearing isopropyl (1), methyl (2), or no substituent (3) on the para position of the benzene ring. A broad spectrum of biological activity as antimicrobial, antiviral, antitumor, cytotoxic, antioxidant, and hemolytic activity was examined. All iodolactones showed bactericidal activity against Proteus mirabilis, and lactones 1,2 were active against Bacillus cereus. The highest cytotoxic activity towards HeLa and MCF7 cancer cell lines and NHDF normal cell line was found for lactone 1. All assessed lactones significantly disrupted antioxidative/oxidative balance of the NHDF, and the most harmful effect was determined by lactone 1. Contrary to lactone 1, lactones 2 and 3 did not induce the hemolysis of erythrocytes after 48 h of incubation. The differences in activity of iodolactones 1–3 in biological tests may be explained by their different impact on physicochemical properties of membrane as the packing order in the hydrophilic area and fluidity of hydrocarbon chains. This was dependent on the presence and type of alkyl substituent. The highest effect on the membrane organization was observed for lactone 1 due to the presence of bulky isopropyl group on the benzene ring.

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Section: Oxidative Stress Markers Analysissupporting

confidence: 93%

Antiproliferative, Antimicrobial and Antiviral Activity of β-Aryl-δ-iodo-γ-lactones, Their Effect on Cellular Oxidative Stress Markers and Biological Membranes

et al. 2020

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“…Inhibitors of NOX enzymes have been shown to slow tumor growth and promote cancer cell death [ 25 , 26 , 27 , 106 , 143 , 209 , 210 ]. The clinical relevance of NOX inhibitors has been further validated in 2019 when the World Health Organization (WHO) acknowledged them as a novel therapeutic class with the root name “naxib” (NADPH oxidase inhibitors).…”

Section: Nox4 As a Therapeutic Target In Cancersmentioning

confidence: 99%

NADPH Oxidase 4 (NOX4) in Cancer: Linking Redox Signals to Oncogenic Metabolic Adaptation

Szántó

2022

IJMS

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Cancer cells can survive and maintain their high proliferation rate in spite of their hypoxic environment by deploying a variety of adaptative mechanisms, one of them being the reorientation of cellular metabolism. A key aspect of this metabolic rewiring is the promotion of the synthesis of antioxidant molecules in order to counter-balance the hypoxia-related elevation of reactive oxygen species (ROS) production and thus combat the onset of cellular oxidative stress. However, opposite to their negative role in the inception of oxidative stress, ROS are also key modulatory components of physiological cellular metabolism. One of the major physiological cellular ROS sources is the NADPH oxidase enzymes (NOX-es). Indeed, NOX-es produce ROS in a tightly regulated manner and control a variety of cellular processes. By contrast, pathologically elevated and unbridled NOX-derived ROS production is linked to diverse cancerogenic processes. In this respect, NOX4, one of the members of the NOX family enzymes, is of particular interest. In fact, NOX4 is closely linked to hypoxia-related signaling and is a regulator of diverse metabolic processes. Furthermore, NOX4 expression and function are altered in a variety of malignancies. The aim of this review is to provide a synopsis of our current knowledge concerning NOX4-related processes in the oncogenic metabolic adaptation of cancer cells.

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“…Importantly, there was a signi cant increment of apoptosis in cells harboring NOX4 di ciency compared with previously drugs or serum-starvation-induced apoptosis (Figure 2A), which supports an inhibited role of NOX4 in the chemotherapeutic drugs-elicited cell death in either starved or normal PTC cells. ROS generated by NOX4 was indispensable for metabolism and secretion of PTC cells [10,23], we then asked whether the effect of NOX4 on drug-induced cell death is mediated by ROS. BCPAP and TPC-1 cells were treated with NAC (a ROS scavenger) and etoposide respectively or combinedly in completed medium.…”

Section: Nox4 Depends On Ros To Oppose Chemotherapeutic Drugs-induced Apoptosismentioning

confidence: 99%

Targeting NOX4 Disrupts the Resistance of Papillary Thyroid Carcinoma to Chemotherapeutic Drugs and Lenvatinib

Tang

Sheng

Peng

et al. 2021

Preprint

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Background: Advanced differentiated thyroid cancer cells are subjected to extreme nutritional starvation which contributes to develop resistance to treatments; however, the underlying mechanism remains unclear.Methods: We used 0.5% serum to mimic starvation during cell culture. A CCK8 assay, cell death Detection ELISAPLUS kit, PI staining were measured to determine cell viability, cell apoptosis and cell cycle respectively in BCPAP cells and TPC-1 cells expressing shRNA against NOX4. The cells were then treated with etoposide and doxorubicin, two chemotherapeutic drugs, as well as lenvatinib to determine the role of NOX4 in resistance. Lenvatinib-resistant BCPAP cells (LRBCs) were also established to confirm the role. Finally, GLX351322, a chemical inhibitor targeting NOX4, was used to inhibit NOX4-derived ROS and detect the the contribution of NOX4 to resistance in vitro and in vivo. Results: NADPH oxidase 4 (NOX4) is highly expressed under serum starvation in BCPAP or TPC-1 cells. NOX4 knockdown impairs cell viability, increases cell apoptosis, extends G1 phase in cell cycle and modulates the level of energy-associated metabolites in starved cells. When these starved cells or Lenvatinib-resistant BCPAP cells (LRBCs) are treated with chemotherapeutic drugs or Lenvatinib, NOX4 knockdown inhibits cell viability and aggravates cell apoptosis depending on NOX4-derived ROS production. GLX351322, a NOX4-derived ROS inhibitor, has a significantly inhibitory effect on cell growth in vitro and the growth of BPCPA-derived even LRBCs-derived xenografts in vivo.Conclusions: These findings highlight NOX4 and NOX4-derived ROS as a potential therapeutic target in resistance of PTC patients.

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Regulation of NADPH oxidase NOX4 by delta iodolactone (IL-δ) in thyroid cancer cells

Cited by 10 publications

References 41 publications

Antiproliferative, Antimicrobial and Antiviral Activity of β-Aryl-δ-iodo-γ-lactones, Their Effect on Cellular Oxidative Stress Markers and Biological Membranes

Antiproliferative, Antimicrobial and Antiviral Activity of β-Aryl-δ-iodo-γ-lactones, Their Effect on Cellular Oxidative Stress Markers and Biological Membranes

NADPH Oxidase 4 (NOX4) in Cancer: Linking Redox Signals to Oncogenic Metabolic Adaptation

Targeting NOX4 Disrupts the Resistance of Papillary Thyroid Carcinoma to Chemotherapeutic Drugs and Lenvatinib

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