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Oxidative Stress and Inflammation in Cancer

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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 29605

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Prof. Dr. Daniela Sorriento

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Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy
Interests: molecular mechanisms of cardiovascular diseases and cancer; intracellular signaling; mitochondrial function; endothelial function; beta-adrenergic receptors; oxidative stress; inflammation; mechanisms of cardiac damage in response to anti-cancer drugs and Fabry disease

Special Issue Information

Dear Colleagues,

Oxidative stress due to the excessive production of reactive oxygen species (ROS) activates pro-inflammatory pathways that are involved in many pathologic conditions, such as diabetes, cardiovascular, cancer, and autoimmune diseases. In particular, several studies suggest the existence of functional crosstalk between chronic inflammation and cancer. Oxidative stress induces the activation of pro-inflammatory transcription factors, leading to a significant increase in inflammatory molecules, which contributes to the development of an inflammatory tumor environment. Inflammation predisposes a patient to the development of cancer and promotes all stages of tumorigenesis, favoring tumor cell proliferation, survival, and migration. Some molecular mechanisms that mediate this crosstalk have been elucidated, leading to the identification of several effectors, such as transcription factors (NFkappaB, AP-1, p53, HIF-1α, PPAR-γ, β-catenin/Wnt, Nrf2) and protein kinases (GRKs, PI3K, MAPK), but other molecular and cellular mechanisms remain to be clarified. Based on these findings, it is likely that targeting inflammation could be a promising strategy for cancer prevention and treatment. In this context, the design and synthesis of specific molecules/drugs that inhibit the inflammatory triggers of cancer could be useful for therapeutic purposes. Moreover, the identification of specific biomarkers could be promising for cancer prevention. Contributions aimed at increasing the knowledge of the molecular mechanisms that are involved in the crosstalk between inflammation and cancer or suggest novel diagnostic and therapeutic strategies are welcome.

Prof. Dr. Daniela Sorriento
Guest Editor

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Keywords

Inflammation
Oxidative stress
Cancer
Inflammatory pathways
Molecular mechanisms
Inflammatory pathway inhibitors

Published Papers (11 papers)

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Research

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14 pages, 2631 KiB

Open AccessArticle

Single-Cell Kinetic Modeling of β-Lapachone Metabolism in Head and Neck Squamous Cell Carcinoma

by Andrew D. Raddatz, Cristina M. Furdui, Erik A. Bey and Melissa L. Kemp

Antioxidants 2023, 12(3), 741; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12030741 - 17 Mar 2023

Viewed by 1650

Abstract

Head and neck squamous cell carcinoma (HNSCC) cells are highly heterogeneous in their metabolism and typically experience elevated reactive oxygen species (ROS) levels such as superoxide and hydrogen peroxide (H₂O₂) in the tumor microenvironment. Tumor cells survive under these chronic oxidative conditions by upregulating antioxidant systems. To investigate the heterogeneity of cellular responses to chemotherapeutic H₂O₂ generation in tumor and healthy tissue, we leveraged single-cell RNA-sequencing (scRNA-seq) data to perform redox systems-level simulations of quinone-cycling β-lapachone treatment as a source of NQO1-dependent rapid superoxide and hydrogen peroxide (H₂O₂) production. Transcriptomic data from 10 HNSCC patient tumors was used to populate over 4000 single-cell antioxidant enzymatic network models of drug metabolism. The simulations reflected significant systems-level differences between the redox states of healthy and cancer cells, demonstrating in some patient samples a targetable cancer cell population or in others statistically indistinguishable effects between non-malignant and malignant cells. Subsequent multivariate analyses between healthy and malignant cellular models pointed to distinct contributors of redox responses between these phenotypes. This model framework provides a mechanistic basis for explaining mixed outcomes of NAD(P)H:quinone oxidoreductase 1 (NQO1)-bioactivatable therapeutics despite the tumor specificity of these drugs as defined by NQO1/catalase expression and highlights the role of alternate antioxidant components in dictating drug-induced oxidative stress. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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28 pages, 11121 KiB

Open AccessArticle

Study of Ferroptosis Transmission by Small Extracellular Vesicles in Epithelial Ovarian Cancer Cells

by Carmen Alarcón-Veleiro, Rocío Mato-Basalo, Sergio Lucio-Gallego, Andrea Vidal-Pampín, María Quindós-Varela, Thamer Al-Qatarneh, Germán Berrecoso, Ángel Vizoso-Vázquez, María C. Arufe and Juan Fafián-Labora

Antioxidants 2023, 12(1), 183; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12010183 - 12 Jan 2023

Cited by 4 | Viewed by 2370

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. The current treatment for EOC involves surgical debulking of the tumors followed by a combination of chemotherapy. While most patients achieve complete remission, many EOCs will recur and develop chemo-resistance. The cancer cells can adapt to several stress stimuli, becoming resistant. Because of this, new ways to fight resistant cells during the disease are being studied. However, the clinical outcomes remain unsatisfactory. Recently, ferroptosis, a novel form of regulated cell death trigged by the accumulation of iron and toxic species of lipid metabolism in cells, has emerged as a promising anti-tumor strategy for EOC treatment. This process has a high potential to become a complementary treatment to the current anti-tumor strategies to eliminate resistant cells and to avoid relapse. Cancer cells, like other cells in the body, release small extracellular vesicles (sEV) that allow the transport of substances from the cells themselves to communicate with their environment. To achieve this, we analyzed the capacity of epithelial ovarian cancer cells (OVCA), treated with ferroptosis inducers, to generate sEV, assessing their size and number, and study the transmission of ferroptosis by sEV. Our results reveal that OVCA cells treated with ferroptotic inducers can modify intercellular communication by sEV, inducing cell death in recipient cells. Furthermore, these receptor cells are able to generate a greater amount of sEV, contributing to a much higher ferroptosis paracrine transmission. Thus, we discovered the importance of the sEV in the communication between cells in OVCA, focusing on the ferroptosis process. These findings could be the beginning form to study the molecular mechanism ferroptosis transmission through sEV. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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17 pages, 4081 KiB

Open AccessArticle

The Protective Anticancer Effect of Natural Lycopene Supercritical CO₂ Watermelon Extracts in Adenocarcinoma Lung Cancer Cells

by Caterina Di Sano, Valentina Lazzara, Miriana Durante, Claudia D’Anna, Angela Bonura, Paola Dino, Carina Gabriela Uasuf, Elisabetta Pace, Marcello Salvatore Lenucci and Andreina Bruno

Antioxidants 2022, 11(6), 1150; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11061150 - 11 Jun 2022

Cited by 9 | Viewed by 2500

Abstract

Carotenoids may have different effects on cancer and its progression. The safety of carotenoid supplements was evaluated in vitro on human non-small cell lung cancer (NSCLC) adenocarcinoma A549 cells by the administration of three different oleoresins containing lycopene and other lipophilic phytochemicals, such as tocochromanols. The oleoresins, obtained by the supercritical CO₂ green extraction technology from watermelon (Lyc W), gấc(Lyc G) and tomato (Lyc T) and chlatrated in α-cyclodextrins, were tested in comparison to synthetic lycopene (Lyc S), by cell cycle, Annexin V-FITC/PI, clonogenic test, Mytosox, intracellular ROS, Western Blot for NF-kB and RT-PCR and ELISA for IL-8. The extracts administered at the same lycopene concentration (10 µM) showed conflicting behaviors: Lyc W, with the highest lycopene/tocochromanols ratio, significantly increased cell apoptosis, mitochondrial stress, intracellular ROS, NF-kB and IL-8 expression and significantly decreased cell proliferation, whereas Lyc G and Lyc T significantly increased only cell proliferation. Lyc S treatment was ineffective. The highest amount of lycopene in Lyc W was able to counteract and revert the cell survival effect of tocochromanols supporting the importance of evaluating the lycopene bio-availability and the real effect of antioxidant tocochromanols’ supplementation which may not only have no anticancer benefits but may even increase cancer aggressivity. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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15 pages, 2840 KiB

Open AccessArticle

Cisplatin-Induced Reproductive Toxicity and Oxidative Stress: Ameliorative Effect of Kinetin

by Rania Abdel-Latif, Moustafa Fathy, Hend Ali Anwar, Muhammad Naseem, Thomas Dandekar and Eman M. Othman

Antioxidants 2022, 11(5), 863; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11050863 - 28 Apr 2022

Cited by 15 | Viewed by 2864

Abstract

Cisplatin is a commonly used chemotherapeutic agent; however, its potential side effects, including gonadotoxicity and infertility, are a critical problem. Oxidative stress has been implicated in the pathogenesis of cisplatin-induced testicular dysfunction. We investigated whether kinetin use at different concentrations could alleviate gonadal injury associated with cisplatin treatment, with an exploration of the involvement of its antioxidant capacity. Kinetin was administered in different doses of 0.25, 0.5, and 1 mg/kg, alone or along with cisplatin for 10 days. Cisplatin toxicity was induced via a single IP dose of 7 mg/kg on day four. In a dose-dependent manner, concomitant administration of kinetin with cisplatin significantly restored testicular oxidative stress parameters, corrected the distorted sperm quality parameters and histopathological changes, enhanced levels of serum testosterone and testicular StAR protein expression, as well as reduced the up-regulation of testicular TNF-α, IL-1β, Il-6, and caspase-3, caused by cisplatin. It is worth noting that the testicular protective effect of the highest kinetin dose was comparable/more potent and significantly higher than the effects of vitamin C and the lowest kinetin dose, respectively. Overall, these data indicate that kinetin may offer a promising approach for alleviating cisplatin-induced reproductive toxicity and organ damage, via ameliorating oxidative stress and reducing inflammation and apoptosis. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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11 pages, 1987 KiB

Open AccessArticle

Oxidative Stress Markers Are Associated with a Poor Prognosis in Patients with Pancreatic Cancer

by Miguel A. Ortega, Oscar Fraile-Martinez, Leonel Pekarek, Cielo García-Montero, Miguel Angel Alvarez-Mon, Alejandro J. Castellanos, Natalio García-Honduvilla, Julia Buján, Melchor Alvarez-Mon, Miguel A. Sáez, Luis G. Guijarro and Angel Asúnsolo

Antioxidants 2022, 11(4), 759; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11040759 - 11 Apr 2022

Cited by 6 | Viewed by 1780

Abstract

Pancreatic cancer is a malignancy of rising prevalence, especially in developed countries where dietary patterns and sedentariness favor its onset. This malady ranks seventh in cancer-related deaths in the world, although it is expected to rank second in the coming years, behind lung cancer. The low survival rate is due to the asymptomatic course of the early stages, which in many cases leads to metastases when becoming evident in advanced stages. In this context, molecular pathology is on the way towards finding new approaches with biomarkers that allow a better prognosis and monitoring of patients. So the present study aims to evaluate a series of molecular biomarkers, PARP1, NOX1, NOX2, eNOS and iNOS, as promising candidates for prognosis and survival by using immunohistochemistry. The analysis performed in 41 patients with pancreatic cancer showed a correlation between a high expression of all these components with a low survival rate, with high statistical power for all. In addition, a 60-month longitudinal surveillance program was managed, accompanied by several clinical parameters. The derivative Kaplan–Meier curves indicated a low cumulative survival rate as well. Ultimately, our research emphasized the value of these molecules as survival-associated biomarkers in pancreatic cancer, offering new gates for clinical management. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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19 pages, 6933 KiB

Open AccessArticle

Piperine Attenuates Lithocholic Acid-Stimulated Interleukin-8 by Suppressing Src/EGFR and Reactive Oxygen Species in Human Colorectal Cancer Cells

by Shinan Li, Thi Thinh Nguyen, Trong Thuan Ung, Dhiraj Kumar Sah, Seon Young Park, Vinoth-Kumar Lakshmanan and Young Do Jung

Antioxidants 2022, 11(3), 530; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11030530 - 10 Mar 2022

Cited by 7 | Viewed by 3165

Abstract

Piperine, a natural alkaloidal pungent product present in pepper plants, possesses the properties of anti-inflammatory and anti-metastasis. Lithocholic acid is a monohydroxy-5beta-cholanic acid with an alpha-hydroxy substituent at position 3; it is a secondary bile acid that plays a pivotal role in fat absorption, and has been discovered to mediate colorectal cancer (CRC) cell invasion and migration. However, the effect of piperine on angiogenesis has been poorly investigated. In the current study, we examined the role of piperine on LCA-stimulated angiogenesis by measuring interleukin-8 (IL-8) expression; moreover, we revealed the potential molecular mechanisms in CRC cells. Here, we showed that piperine inhibited LCA-stimulated endothelial EA.hy926 cell angiogenesis in a conditioned medium obtained from colorectal HCT-116 cells. Experiments with an IL-8 neutralizer showed that IL-8 present in the conditioned medium was the major angiogenic factor. Piperine inhibited LCA-stimulated ERK1/2 and AKT via the Src/EGFR-driven ROS signaling pathway in the colorectal cell line (HCT-116). Through mutagenesis and inhibitory studies, we revealed that ERK1/2 acted as an upstream signaling molecule in AP-1 activation, and AKT acted as an upstream signaling molecule in NF-κB activation, which in turn attenuated IL-8 expression. Taken together, we demonstrated that piperine blocked LCA-stimulated IL-8 expression by suppressing Src and EGFR in human CRC HCT-116 cells, thus remarkably attenuating endothelial EA.hy926 cell tube formation. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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Review

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22 pages, 4388 KiB

Open AccessReview

Advanced Delivery System of Polyphenols for Effective Cancer Prevention and Therapy

by Koung Hee Kim, Mi-Ran Ki, Ki Ha Min and Seung Pil Pack

Antioxidants 2023, 12(5), 1048; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12051048 - 05 May 2023

Cited by 11 | Viewed by 2581

Abstract

Polyphenols from plants such as fruits and vegetables are phytochemicals with physiological and pharmacological activity as potential drugs to modulate oxidative stress and inflammation associated with cardiovascular disease, chronic disease, and cancer. However, due to the limited water solubility and bioavailability of many natural compounds, their pharmacological applications have been limited. Researchers have made progress in the development of nano- and micro-carriers that can address these issues and facilitate effective drug delivery. The currently developed drug delivery systems maximize the fundamental effects in various aspects such as absorption rate, stability, cellular absorption, and bioactivity of polyphenols. This review focuses on the antioxidant and anti-inflammatory effects of polyphenols enhanced by the introduction of drug delivery systems, and ultimately discusses the inhibition of cancer cell proliferation, growth, and angiogenesis. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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20 pages, 1316 KiB

Open AccessReview

Epigenetics and Metabolism Reprogramming Interplay into Glioblastoma: Novel Insights on Immunosuppressive Mechanisms

by Filippo Torrisi, Simona D’Aprile, Simona Denaro, Anna Maria Pavone, Cristiana Alberghina, Agata Zappalà, Rosario Giuffrida, Lucia Salvatorelli, Giuseppe Broggi, Gaetano Giuseppe Magro, Vittorio Calabrese, Nunzio Vicario and Rosalba Parenti

Antioxidants 2023, 12(2), 220; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12020220 - 18 Jan 2023

Cited by 4 | Viewed by 2385

Abstract

The central nervous system represents a complex environment in which glioblastoma adapts skillfully, unleashing a series of mechanisms suitable for its efficient development and diffusion. In particular, changes in gene expression and mutational events that fall within the domain of epigenetics interact complexly with metabolic reprogramming and stress responses enacted in the tumor microenvironment, which in turn fuel genomic instability by providing substrates for DNA modifications. The aim of this review is to analyze this complex interaction that consolidates several conditions that confer a state of immunosuppression and immunoevasion, making glioblastoma capable of escaping attack and elimination by immune cells and therefore invincible against current therapies. The progressive knowledge of the cellular mechanisms that underlie the resistance of the glioblastoma represents, in fact, the only weapon to unmask its weak points to be exploited to plan successful therapeutic strategies. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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31 pages, 833 KiB

Open AccessReview

The Adipocyte–Macrophage Relationship in Cancer: A Potential Target for Antioxidant Therapy

by Sofía Sanhueza, Layla Simón, Mariana Cifuentes and Andrew F. G. Quest

Antioxidants 2023, 12(1), 126; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12010126 - 04 Jan 2023

Cited by 6 | Viewed by 3042

Abstract

Obesity has emerged as a major public health concern with a staggering 39% worldwide prevalence as of 2021. Given the magnitude of the problem and considering its association with chronic low-grade systemic inflammation, it does not come as a surprise that obesity is now considered one of the major risk factors for the development of several chronic diseases, such as diabetes, cardiovascular problems, and cancer. Adipose tissue dysfunction in obesity has taken center stage in understanding how changes in its components, particularly adipocytes and macrophages, participate in such processes. In this review, we will initially focus on how changes in adipose tissue upon excess fat accumulation generate endocrine signals that promote cancer development. Moreover, the tumor microenvironment or stroma, which is also critical in cancer development, contains macrophages and adipocytes, which, in reciprocal paracrine communication with cancer cells, generate relevant signals. We will discuss how paracrine signaling in the tumor microenvironment between cancer cells, macrophages, and adipocytes favors cancer development and progression. Finally, as reactive oxygen species participate in many of these signaling pathways, we will summarize the information available on how antioxidants can limit the effects of endocrine and paracrine signaling due to dysfunctional adipose tissue components in obesity. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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21 pages, 860 KiB

Open AccessReview

Modulation of Cellular Redox Parameters for Improving Therapeutic Responses in Multiple Myeloma

by Alessandro Allegra, Claudia Petrarca, Mario Di Gioacchino, Marco Casciaro, Caterina Musolino and Sebastiano Gangemi

Antioxidants 2022, 11(3), 455; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11030455 - 25 Feb 2022

Cited by 12 | Viewed by 2083

Abstract

Raised oxidative stress and abnormal redox status are typical features of multiple myeloma cells, and the identification of the intimate mechanisms that regulate the relationships between neoplastic cells and redox homeostasis may reveal possible new anti-myeloma therapeutic targets to increase the effectiveness of anti-myeloma drugs synergistically or to eradicate drug-resistant clones while reducing toxicity toward normal cells. An alteration of the oxidative state is not only responsible for the onset of multiple myeloma and its progression, but it also appears essential for the therapeutic response and for developing any chemoresistance. Our review aimed to evaluate the literature’s current data on the effects of oxidative stress on the response to drugs generally employed in the therapy of multiple myeloma, such as proteasome inhibitors, immunomodulators, and autologous transplantation. In the second part of the review, we analyzed the possibility of using other substances, often of natural origin, to modulate the oxidative stress to interfere with the progression of myelomatous disease. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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19 pages, 1138 KiB

Open AccessReview

Can Antioxidants Reduce the Toxicity of Bisphenol?

by Wanda Mączka, Małgorzata Grabarczyk and Katarzyna Wińska

Antioxidants 2022, 11(2), 413; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11020413 - 18 Feb 2022

Cited by 7 | Viewed by 3422

Abstract

BPA is still the subject of extensive research due to its widespread use, despite its significant toxicity resulting not only from its negative impact on the endocrine system but also from disrupting the organism’s oxidative homeostasis. At the molecular level, bisphenol A (BPA) causes an increased production of ROS and hence a change in the redox balance, mitochondrial dysfunction, and modulation of cell signaling pathways. Importantly, these changes accumulate in animals and humans, and BPA toxicity may be aggravated by poor diet, metabolic disorders, and coexisting diseases. Accordingly, approaches using antioxidants to counteract the negative effects of BPA are being considered. The preliminary results that are described in this paper are promising, however, it should be emphasized that further studies are required to determine the optimal dosage and treatment regimen to counteract BPA toxicity. It also seems necessary to have a more holistic approach showing, on the one hand, the influence of BPA on the overall human metabolism and, on the other hand, the influence of antioxidants in doses that are acceptable with the diet on BPA toxicity. This is due in part to the fact that in many cases, the positive effect of antioxidants in in vitro studies is not confirmed by clinical studies. For this reason, further research into the molecular mechanisms of BPA activity is also recommended. Full article

(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cancer)

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