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Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy

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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 (15 August 2022) | Viewed by 26408

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Special Issue Editors

Dr. Miguel Alcaraz-Saura

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1. Department of Pediatric, Hospital Clínico Universitario “Virgen de la Arrixaca”, Ctra. Madrid-Cartagena, 30120 Murcia, Spain
2. Instituto Murciano de Investigación Biosanitaria “Virgen de la Arrixaca” (IMIB-Arrixaca), 30100 Murcia, Spain
Interests: nutrition and metabolism in neonatology; probiotics; vitamins; cancer; oxidative stress syndrome; radiation effects; radioprotectors
Special Issues, Collections and Topics in MDPI journals

Dr. Miguel Alcaraz

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Guest Editor

1. Radiology and Physical Medicine Department, School of Medicine, University of Murcia, 30100 Murcia, Spain
2. Instituto Murciano de Investigación Biosanitaria “Virgen de la Arrixaca” (IMIB-Arrixaca), 30100 Murcia, Spain
Interests: ionizing radiation; radiation effects; radiobiology; radiation protection; radiology; radiotherapy; radioprotectors; radiosensitizers; nonionizing radiation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There is a clear need for the development of new nontoxic substances that can reduce the undesirable effects of ionizing radiation during medical application, especially in diagnostic imaging, nuclear medicine and radiation oncology, to protect both patients and professionally exposed workers. Similarly, the industrial use of nuclear energy, the potential risk of nuclear terrorism, as well as the increase in professionals exposed to ionizing radiation have increased interest in this aspect of radiobiology. In addition, the damaging effects of cosmic radiation are seen today as mitigating factors against the development of activities towards space exploration. Finally, the hitherto utopian objective of protecting normal cells while selectively injuring tumor cells when both are in the same vicinity of the radiation field during radiotherapy has stimulated interest in this Special Issue of Antioxidants.

Since the discovery of the first radioprotective substances, sulfhydryl compounds have been found to express radioprotective capacity when present in biological environments before exposure to radiation. Thus far, they constitute the only type of radioprotective substances in clinical use, despite the fact that, in recent years, other substances with higher radioprotective/genoprotective capacities with lower toxicity have been described. Numerous novel substances are being classified as radioprotective, radiomitigating or radiomodulating, portraying a vast spectrum of agents with radioprotective/genoprotective capacities; however, it is difficult to comparatively assess these substances due to the different end points used to study the effects of the radiation doses administered, and the concentrations and procedures used to evaluate their protective capacities.

The objective of this Special Issue of Antioxidants in radiological protection, radiobiology and radiotherapy aims to cover the latest advances in the use of antioxidants in the field of ionizing radiation; of particular interest is their application against nonionizing radiation in these same fields of action.

Dr. Miguel Alcaraz-Saura
Dr. Miguel Alcaraz
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

ionizing radiation
nonionizing radiation
oxidative stress
radioprotectors
radiomitigators
radiosensitizers
antioxidant defenses
cancer therapy

Published Papers (11 papers)

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Research

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13 pages, 3341 KiB

Open AccessArticle

Golgi Phosphoprotein 3 Mediates Radiation-Induced Bystander Effect via ERK/EGR1/TNF-α Signal Axis

by Feng Qin, Guodong Chen, Kwan Ngok Yu, Miaomiao Yang, Wei Cao, Peizhong Kong, Shengjie Peng, Mingyu Sun, Lili Nie and Wei Han

Antioxidants 2022, 11(11), 2172; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11112172 - 01 Nov 2022

Cited by 1 | Viewed by 1652

Abstract

The radiation-induced bystander effect (RIBE), an important non-targeted effect of radiation, has been proposed to be associated with irradiation-caused secondary cancers and reproductive damage beyond the irradiation-treated area after radiotherapy. However, the mechanisms for RIBE signal(s) regulation and transduction are not well understood. In the present work, we found that a Golgi protein, GOLPH3, was involved in RIBE transduction. Knocking down GOLPH3 in irradiated cells blocked the generation of the RIBE, whereas re-expression of GOLPH3 in knockdown cells rescued the RIBE. Furthermore, TNF-α was identified as an important intercellular signal molecule in the GOLPH3-mediated RIBE. A novel signal axis, GOLPH3/ERK/EGR1, was discovered to modulate the transcription of TNF-α and determine the level of released TNF-α. Our findings provide new insights into the molecular mechanism of the RIBE and a potential target for RIBE modulation. Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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24 pages, 3716 KiB

Open AccessArticle

Paradoxical Radiosensitizing Effect of Carnosic Acid on B16F10 Metastatic Melanoma Cells: A New Treatment Strategy

by Miguel Alcaraz, Amparo Olivares, Marina Andreu-Gálvez, Daniel Gyingiri Achel, Ana María Mercado and Miguel Alcaraz-Saura

Antioxidants 2022, 11(11), 2166; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11112166 - 31 Oct 2022

Cited by 2 | Viewed by 1603

Abstract

Carnosic acid (CA) is a phenolic diterpene characterized by its high antioxidant activity; it is used in industrial, cosmetic, and nutritional applications. We evaluated the radioprotective capacity of CA on cells directly exposed to X-rays and non-irradiated cells that received signals from X-ray treated cells (radiation induced bystander effect, RIBE). The genoprotective capacity was studied by in vivo and in vitro micronucleus assays. Radioprotective capacity was evaluated by clonogenic cell survival, MTT, apoptosis and intracellular glutathione assays comparing radiosensitive cells (human prostate epithelium, PNT2) with radioresistant cells (murine metastatic melanoma, B16F10). CA was found to exhibit a genoprotective capacity in cells exposed to radiation (p < 0.001) and in RIBE (p < 0.01). In PNT2 cells, considered as normal cells in our study, CA achieved 97% cell survival after exposure to 20 Gy of X-rays, eliminating 67% of radiation-induced cell death (p < 0.001), decreasing apoptosis (p < 0.001), and increasing the GSH/GSSH ratio (p < 0.01). However, the administration of CA to B16F10 cells decreased cell survival by 32%, increased cell death by 200% (p < 0.001) compared to irradiated cells, and increased cell death by 100% (p < 0.001) in RIBE bystander cells (p < 0.01). Furthermore, it increased apoptosis (p < 0.001) and decreased the GSH/GSSG ratio (p < 0.01), expressing a paradoxical radiosensitizing effect in these cells. Knowing the potential mechanisms of action of substances such as CA could help to create new applications that would protect healthy cells and exclusively damage neoplastic cells, thus presenting a new desirable strategy for cancer patients in need of radiotherapy. Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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19 pages, 5401 KiB

Open AccessArticle

Effects of Gamma-Tocotrienol on Partial-Body Irradiation-Induced Intestinal Injury in a Nonhuman Primate Model

by Sarita Garg, Tarun K. Garg, Isabelle R. Miousse, Stephen Y. Wise, Oluseyi O. Fatanmi, Alena V. Savenka, Alexei G. Basnakian, Vijay K. Singh and Martin Hauer-Jensen

Antioxidants 2022, 11(10), 1895; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11101895 - 25 Sep 2022

Cited by 8 | Viewed by 1694

Abstract

Exposure to high doses of radiation, accidental or therapeutic, often results in gastrointestinal (GI) injury. To date, there are no therapies available to mitigate GI injury after radiation exposure. Gamma-tocotrienol (GT3) is a promising radioprotector under investigation in nonhuman primates (NHP). We have shown that GT3 has radioprotective function in intestinal epithelial and crypt cells in NHPs exposed to 12 Gy total-body irradiation (TBI). Here, we determined GT3 potential in accelerating the GI recovery in partial-body irradiated (PBI) NHPs using X-rays, sparing 5% bone marrow. Sixteen rhesus macaques were treated with either vehicle or GT3 24 h prior to 12 Gy PBI. Structural injuries and crypt survival were examined in proximal jejunum on days 4 and 7. Plasma citrulline was assessed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Crypt cell proliferation and apoptotic cell death were evaluated using Ki-67 and TUNEL staining. PBI significantly decreased mucosal surface area and reduced villous height. Interestingly, GT3 increased crypt survival and enhanced stem cell proliferation at day 4; however, the effects seemed to be minimized by day 7. GT3 did not ameliorate a radiation-induced decrease in citrulline levels. These data suggest that X-rays induce severe intestinal injury post-PBI and that GT3 has minimal radioprotective effect in this novel model. Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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18 pages, 16517 KiB

Open AccessArticle

Fucoidan/UVC Combined Treatment Exerts Preferential Antiproliferation in Oral Cancer Cells but Not Normal Cells

by Ya-Ting Chuang, Jun-Ping Shiau, Ching-Yu Yen, Ming-Feng Hou, Jiiang-Huei Jeng, Jen-Yang Tang and Hsueh-Wei Chang

Antioxidants 2022, 11(9), 1797; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11091797 - 12 Sep 2022

Cited by 2 | Viewed by 1619

Abstract

Combined treatment is a promising anticancer strategy for improving antiproliferation compared with a single treatment but is limited by adverse side effects on normal cells. Fucoidan (FN), a brown-algae-derived polysaccharide safe food ingredient, exhibits preferential function for antiproliferation to oral cancer but not normal cells. Utilizing the preferential antiproliferation, the impacts of FN in regulating ultraviolet C (UVC) irradiation were assessed in oral cancer cells. A combined treatment (UVC/FN) reduced cell viability of oral cancer cells (Ca9-22 and CAL 27) more than single treatments (FN or UVC), i.e., 53.7%/54.6% vs. 71.2%/91.6%, and 89.2%/79.4%, respectively, while the cell viability of UVC/FN treating on non-malignant oral (S–G) was higher than oral cancer cells, ranging from 106.0 to 108.5%. Mechanistically, UVC/FN preferentially generated higher subG1 accumulation and apoptosis-related inductions (annexin V, caspases 3, 8, and 9) in oral cancer cells than single treatments. UVC/FN preferentially generated higher oxidative stress than single treatments, as evidenced by flow cytometry-detecting reactive oxygen species, mitochondrial superoxide, and glutathione. Moreover, UVC/FN preferentially caused more DNA damage (γH2AX and 8-hydroxy-2’-deoxyguanosine) in oral cancer cells than in single treatments. N-acetylcysteine pretreatment validated the oxidative stress effects in these UVC/FN-induced changes. Taken together, FN effectively enhances UVC-triggered antiproliferation to oral cancer cells. UVC/FN provides a promising potential for preferential and synergistic antiproliferation in antioral cancer therapy. Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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15 pages, 4818 KiB

Open AccessArticle

NRF2 Mediates Cellular Resistance to Transformation, Radiation, and Inflammation in Mice

by Dörthe Schaue, Ewa D. Micewicz, Josephine A. Ratikan, Keisuke S. Iwamoto, Erina Vlashi, J. Tyson McDonald and William H. McBride

Antioxidants 2022, 11(9), 1649; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11091649 - 25 Aug 2022

Cited by 3 | Viewed by 2208

Abstract

Nuclear factor erythroid 2-related factor 2 (NRF2) is recognized as a master transcription factor that regulates expression of numerous detoxifying and antioxidant cytoprotective genes. In fact, models of NRF2 deficiency indicate roles not only in redox regulation, but also in metabolism, inflammatory/autoimmune disease, cancer, and radioresistancy. Since ionizing radiation (IR) generates reactive oxygen species (ROS), it is not surprising it activates NRF2 pathways. However, unexpectedly, activation is often delayed for many days after the initial ROS burst. Here, we demonstrate that, as assayed by γ-H2AX staining, rapid DNA double strand break (DSB) formation by IR in primary mouse Nrf2–/– MEFs was not affected by loss of NRF2, and neither was DSB repair to any great extent. In spite of this, basal and IR-induced transformation was greatly enhanced, suggesting that NRF2 protects against late IR-induced genomic instability, at least in murine MEFs. Another possible IR- and NRF2-related event that could be altered is inflammation and NRF2 deficiency increased IR-induced NF-κB pro-inflammatory responses mostly late after exposure. The proclivity of NRF2 to restrain inflammation is also reflected in the reprogramming of tumor antigen-specific lymphocyte responses in mice where Nrf2 k.o. switches Th2 responses to Th1 polarity. Delayed NRF2 responses to IR may be critical for the immune transition from prooxidant inflammation to antioxidant healing as well as in driving cellular radioresistance and survival. Targeting NRF2 to reprogram immunity could be of considerable therapeutic benefit in radiation and immunotherapy. Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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16 pages, 3427 KiB

Open AccessArticle

A Dietary Antioxidant Formulation Ameliorates DNA Damage Caused by γ-Irradiation in Normal Human Bronchial Epithelial Cells In Vitro

by J. P. Jose Merlin, Sabateeshan Mathavarajah, Graham Dellaire, Kieran P. J. Murphy and H. P. Vasantha Rupasinghe

Antioxidants 2022, 11(7), 1407; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11071407 - 20 Jul 2022

Cited by 5 | Viewed by 2239

Abstract

Antioxidants can be used as radioprotectants to reduce DNA damage due to exposure to radiation that could result in malignancies, including lung cancer. Mortality rates are consistently higher in lung cancer, which is usually diagnosed at later stages of cancer development and progression. In this preliminary study, we examined the potential of an antioxidant formulation (AOX2) to reduce DNA damage using a cell model of human normal bronchial epithelial cells (BEAS-2B). Cells were exposed to γ-irradiation or smoke-related hydrocarbon 4[(acetoxymethyl)nitrosamino]-1 (3-pyridyl) 1-butanone (NNKOAc) to induce DNA damage. We monitored intracellular reactive oxygen species (ROS) levels and evidence of genotoxic damage including DNA fragmentation ELISA, γ-H2AX immunofluorescence, and comet assays. Pre-incubation of the cells with AOX2 before exposure to γ-irradiation and NNKOAc significantly reduced DNA damage. The dietary antioxidant preparation AOX2 significantly reduced the induction of the tumor suppressor protein p53 and DNA damage-associated γ-H2AX phosphorylation by radiation and the NNKOAc treatment. Thus, AOX2 has the potential to act as a chemoprotectant by lowering ROS levels and DNA damage caused by exposure to radiation or chemical carcinogens. Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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12 pages, 2361 KiB

Open AccessArticle

Effect of Low-Dose Radiotherapy on the Circulating Levels of Paraoxonase-1-Related Variables and Markers of Inflammation in Patients with COVID-19 Pneumonia

by Elisabet Rodríguez-Tomàs, Johana C. Acosta, Laura Torres-Royo, Gabriel De Febrer, Gerard Baiges-Gaya, Helena Castañé, Andrea Jiménez, Carlos Vasco, Pablo Araguas, Junior Gómez, Bárbara Malave, Miguel Árquez, David Calderón, Berta Piqué, Manel Algara, Ángel Montero, Josep M. Simó, Xavier Gabaldó-Barrios, Sebastià Sabater, Jordi Camps, Jorge Joven and Meritxell Arenas Show full author list Hide full author list

Antioxidants 2022, 11(6), 1184; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11061184 - 16 Jun 2022

Cited by 6 | Viewed by 2236

Abstract

The aim of our study was to investigate the changes produced by low-dose radiotherapy (LDRT) in the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1) and inflammatory markers in patients with COVID-19 pneumonia treated with LDRT and their interactions with clinical and radiological changes. Data were collected from the IPACOVID prospective clinical trial (NCT04380818). The study included 30 patients treated with a whole-lung dose of 0.5 Gy. Clinical follow-up, as well as PON1-related variables, cytokines, and radiological parameters were analyzed before LDRT, at 24 h, and 1 week after treatment. Twenty-five patients (83.3%) survived 1 week after LDRT. Respiratory function and radiological images improved in survivors. Twenty-four hours after LDRT, PON1 concentration significantly decreased, while transforming growth factor beta 1 (TGF-β1) increased with respect to baseline. One week after LDRT, patients had increased PON1 activities and lower PON1 and TGF-β1 concentrations compared with 24 h after LDRT, PON1 specific activity increased, lactate dehydrogenase (LDH), and C-reactive protein (CRP) decreased, and CD4+ and CD8+ cells increased after one week. Our results highlight the benefit of LDRT in patients with COVID-19 pneumonia and it might be mediated, at least in part, by an increase in serum PON1 activity at one week and an increase in TGF-β1 concentrations at 24 h. Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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24 pages, 4688 KiB

Open AccessArticle

Genoprotective Effect of Some Flavonoids against Genotoxic Damage Induced by X-rays In Vivo: Relationship between Structure and Activity

by Miguel Alcaraz, Amparo Olivares, Daniel Gyingiri Achel, José Antonio García-Gamuz, Julián Castillo and Miguel Alcaraz-Saura

Antioxidants 2022, 11(1), 94; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11010094 - 30 Dec 2021

Cited by 16 | Viewed by 2285

Abstract

Flavonoids constitute a group of polyphenolic compounds characterized by a common gamma-benzo- pyrone structure considered in numerous biological systems to possess antioxidant capacity. Among the different applications of flavonoids, its genoprotective capacity against damage induced by ionizing radiation stands out, which has been related to antioxidant activity and its chemical structure. In this study, we determined the frequency of appearance of micronucleus in vivo by means of the micronucleus assay. This was conducted in mice treated with different flavonoids before and after exposure to 470 mGy X-rays; thereafter, their bone marrow polychromatophilic erythrocytes were evaluated to establish the structural factors enhancing the observed genoprotective effect. Our results in vivo show that the presence of a monomeric flavan-3-ol type structure, with absence of carbonyl group in position C4 of ring C, absence of conjugation between the carbons bearing the C2 = C3 double bond and the said ring, presence of a catechol group in ring B and characteristic hydroxylation in positions 5 and 7 of ring A are the structural characteristics that determine the highest degree of genoprotection. Additionally, a certain degree of polymerization of this flavonoid monomer, but maintaining significant levels of monomers and dimers, contributes to increasing the degree of genoprotection in the animals studied at both times of their administration (before and after exposure to X-rays). Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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18 pages, 2957 KiB

Open AccessArticle

Gut Microbiota-Derived PGF2α Fights against Radiation-Induced Lung Toxicity through the MAPK/NF-κB Pathway

by Zhi-Yuan Chen, Hui-Wen Xiao, Jia-Li Dong, Yuan Li, Bin Wang, Sai-Jun Fan and Ming Cui

Antioxidants 2022, 11(1), 65; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11010065 - 28 Dec 2021

Cited by 19 | Viewed by 2688

Abstract

Radiation pneumonia is a common and intractable side effect associated with radiotherapy for chest cancer and involves oxidative stress damage and inflammation, prematurely halting the remedy and reducing the life quality of patients. However, the therapeutic options for the complication have yielded disappointing results in clinical application. Here, we report an effective avenue for fighting against radiation pneumonia. Faecal microbiota transplantation (FMT) reduced radiation pneumonia, scavenged oxidative stress and improved lung function in mouse models. Local chest irradiation shifted the gut bacterial taxonomic proportions, which were preserved by FMT. The level of gut microbiota-derived PGF2α decreased following irradiation but increased after FMT. Experimental mice with PGF2α replenishment, via an oral route, exhibited accumulated PGF2α in faecal pellets, peripheral blood and lung tissues, resulting in the attenuation of inflammatory status of the lung and amelioration of lung respiratory function following local chest irradiation. PGF2α activated the FP/MAPK/NF-κB axis to promote cell proliferation and inhibit apoptosis with radiation challenge; silencing MAPK attenuated the protective effect of PGF2α on radiation-challenged lung cells. Together, our findings pave the way for the clinical treatment of radiotherapy-associated complications and underpin PGF2α as a gut microbiota-produced metabolite. Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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18 pages, 4429 KiB

Open AccessArticle

MnTnHex-2-PyP⁵⁺, Coupled to Radiation, Suppresses Metastasis of 4T1 and MDA-MB-231 Breast Cancer via AKT/Snail/EMT Pathways

by Sung-Won Shin, Changhoon Choi, Hakyoung Kim, Yeeun Kim, Sohee Park, Shin-Yeong Kim, Ines Batinic-Haberle and Won Park

Antioxidants 2021, 10(11), 1769; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10111769 - 05 Nov 2021

Cited by 10 | Viewed by 2804

Abstract

Tumor migration and invasion induced by the epithelial-to-mesenchymal transition (EMT) are prerequisites for metastasis. Here, we investigated the inhibitory effect of a mimic of superoxide dismutase (SOD), cationic Mn(III) ortho-substituted N-n-hexylpyridylporphyrin (MnTnHex-2-PyP⁵⁺, MnHex) on the metastasis of breast cancer in cellular and animal models, focusing on the migration of tumor cells and the factors that modulate this behavior. Wound healing and Transwell migration assays revealed that the migration of mouse mammary carcinoma 4T1 cells was markedly reduced during the concurrent treatment of MnHex and radiation therapy (RT) compared with that of the control and RT alone. Bioluminescence imaging showed that MnHex/RT co-treatment dramatically reduced lung metastasis of 4T1 cells in mice, compared with the sham control and both single treatments. Western blotting and immunofluorescence showed that MnHex treatment of 4T1 cells reversed the RT-induced EMT via inhibiting AKT/GSK-3β/Snail pathway in vitro, thereby decreasing cell migration and invasion. Consistently, histopathological analyses of 4T1 tumors showed that MnHex/RT reduced Snail expression, blocked EMT, and in turn suppressed metastases. Again, in the human metastatic breast cancer MDA-MB-231 cell line, MnHex inhibited metastatic potential in vitro and in vivo and suppressed the RT-induced Snail expression. In addition to our previous studies showing tumor growth inhibition, this study demonstrated that MnHex carries the ability to minimize the metastatic potential of RT-treated cancers, thus overcoming their radioresistance. Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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Review

Jump to: Research

20 pages, 1535 KiB

Open AccessReview

Phytochemicals: Potential Therapeutic Modulators of Radiation Induced Signaling Pathways

by Bimal Prasad Jit, Biswajita Pradhan, Rutumbara Dash, Prajna Paramita Bhuyan, Chhandashree Behera, Rajendra Kumar Behera, Ashok Sharma, Miguel Alcaraz and Mrutyunjay Jena

Antioxidants 2022, 11(1), 49; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11010049 - 27 Dec 2021

Cited by 18 | Viewed by 3853

Abstract

Ionizing radiation results in extensive damage to biological systems. The massive amount of ionizing radiation from nuclear accidents, radiation therapy (RT), space exploration, and the nuclear battlefield leads to damage to biological systems. Radiation injuries, such as inflammation, fibrosis, and atrophy, are characterized by genomic instability, apoptosis, necrosis, and oncogenic transformation, mediated by the activation or inhibition of specific signaling pathways. Exposure of tumors or normal cells to different doses of ionizing radiation could lead to the generation of free radical species, which can release signal mediators and lead to harmful effects. Although previous FDA-approved agents effectively mitigate radiation-associated toxicities, their use is limited due to their high cellular toxicities. Preclinical and clinical findings reveal that phytochemicals derived from plants that exhibit potent antioxidant activities efficiently target several signaling pathways. This review examined the prospective roles played by some phytochemicals in altering signal pathways associated with radiation response. Full article

(This article belongs to the Special Issue Antioxidants in Radiation Protection, Radiobiology and Radiation Therapy)

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