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Chen Y, Liu X, Chen B, Zhu F, Wang Z, Cheong KL, Ye S, Zhong S, Chen J. Selenium nanoparticles decorated by fucoidan induce ferroptosis in HepG2 cells. Int J Biol Macromol 2025; 289:138841. [PMID: 39701247 DOI: 10.1016/j.ijbiomac.2024.138841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 12/12/2024] [Accepted: 12/15/2024] [Indexed: 12/21/2024]
Abstract
Unlike apoptosis, necrosis and autophagy, ferroptosis is a novel type of regulated cell death, and the mechanism by which selenium nanoparticles induce ferroptosis in cancer cells has rarely been investigated. To investigate the mechanism of inhibition of HepG2 cell proliferation by fucoidan-selenium nanoparticles (FD-SeNPs) by inducing ferroptosis. The mechanism was explored by detecting ROS, MDA, GSH and Fe2+ and utilizing TEM and Western blot assay. The results showed that FD-SeNPs increased intracellular ROS, MDA and Fe2+ levels and decreased GSH levels. Moreover, HepG2 cells treated with FD-SeNPs showed mitochondrial shrinkage, volume reduction and mitochondrial cristae breakage. The ability to reverse the changes in the above indexes after Ferrostatin-1 (Fer-1) intervention suggests that FD-SeNPs inhibit HepG2 cell proliferation by inducing cells to undergo ferroptosis. Further mechanistic studies revealed that FD-SeNPs decreased the expression of Nrf2, HO-1, SLC7A11 (xCT), GCLC and GPX4 proteins to promote lipid peroxidation in HepG2 cells. Moreover, FD-SeNPs could disrupt intracellular iron homeostasis by up-regulating transferrin protein and down-regulating SLC40A1 and Ferritin proteins, suggesting that FD-SeNPs induced cells to undergo ferroptosis by regulating proteins related to lipid peroxidation and iron homeostasis. This study provides theoretical data for reference in applying FD-SeNPs in developing anti-cancer clinical drugs.
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Affiliation(s)
- Yanzhe Chen
- College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Zhanjiang 524088, China
| | - Xiaofei Liu
- College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Zhanjiang 524088, China
| | - Bowen Chen
- College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Zhanjiang 524088, China
| | - Feifei Zhu
- College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Zhanjiang 524088, China
| | - Zhuo Wang
- College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Zhanjiang 524088, China
| | - Kit-Leong Cheong
- College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Zhanjiang 524088, China
| | - Shengquan Ye
- College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Zhanjiang 524088, China
| | - Saiyi Zhong
- College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Zhanjiang 524088, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China
| | - Jianping Chen
- College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, Key Laboratory of Advanced Processing of Aquatic Product of Guangdong Higher Education Institution, Zhanjiang 524088, China; Guangdong Provincial Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan 528000, China.
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Famurewa AC, George MY, Ukwubile CA, Kumar S, Kamal MV, Belle VS, Othman EM, Pai SRK. Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity-a review of literature evidence. Biometals 2024; 37:1325-1378. [PMID: 39347848 DOI: 10.1007/s10534-024-00637-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 08/30/2024] [Indexed: 10/01/2024]
Abstract
Anticancer chemotherapy (ACT) remains a cornerstone in cancer treatment, despite significant advances in pharmacology over recent decades. However, its associated side effect toxicity continues to pose a major concern for both oncology clinicians and patients, significantly impacting treatment protocols and patient quality of life. Current clinical strategies to mitigate ACT-induced toxicity have proven largely unsatisfactory, leaving a critical unmet need to block toxicity mechanisms without diminishing ACT's therapeutic efficacy. This review aims to document the molecular mechanisms underlying ACT toxicity and highlight research efforts exploring the protective effects of trace elements (TEs) and their nanoparticles (NPs) against these mechanisms. Our literature review reveals that the primary driver of ACT toxicity is redox imbalance, which triggers oxidative inflammation, apoptosis, endoplasmic reticulum stress, mitochondrial dysfunction, autophagy, and dysregulation of signaling pathways such as PI3K/mTOR/Akt. Studies suggest that TEs, including zinc, selenium, boron, manganese, and molybdenum, and their NPs, can potentially counteract ACT-induced toxicity by inhibiting oxidative stress-mediated pathways, including NF-κB/TLR4/MAPK/NLRP3, STAT-3/NLRP3, Bcl-2/Bid/p53/caspases, and LC3/Beclin-1/CHOP/ATG6, while also upregulating protective signaling pathways like Sirt1/PPAR-γ/PGC-1α/FOXO-3 and Nrf2/HO-1/ARE. However, evidence regarding the roles of lncRNA and the Wnt/β-catenin pathway in ACT toxicity remains inconsistent, and the impact of TEs and NPs on ACT efficacy is not fully understood. Further research is needed to confirm the protective effects of TEs and their NPs against ACT toxicity in cancer patients. In summary, TEs and their NPs present a promising avenue as adjuvant agents for preventing non-target organ toxicity induced by ACT.
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Affiliation(s)
- Ademola C Famurewa
- Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Medical Sciences, Alex Ekwueme Federal University Ndufu-Alike Ikwo, Abakaliki, Ebonyi, Nigeria.
- Centre for Natural Products Discovery, School of P harmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
- Department of Pharmacology, Manipal College of Pharmaceutical Science, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
| | - Mina Y George
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Cletus A Ukwubile
- Department of Pharmacognosy, Faculty of Pharmacy, University of Maiduguri, Bama Road, Maiduguri, Borno, Nigeria
| | - Sachindra Kumar
- Department of Pharmacology, Manipal College of Pharmaceutical Science, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Mehta V Kamal
- Department of Biochemistry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Vijetha S Belle
- Department of Biochemistry, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Eman M Othman
- Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt
- Cancer Therapy Research Center, Department of Biochemistry-I, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany
- Department of Bioinformatics, University of Würzburg, Am Hubland, 97074, BiocenterWürzburg, Germany
| | - Sreedhara Ranganath K Pai
- Department of Pharmacology, Manipal College of Pharmaceutical Science, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
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Xu C, Zhao S, Li Z, Pan J, Zhou Y, Hu Q, Zou Y. Identification of altered metabolic functional components using metabolomics to analyze the different ages of fruiting bodies of Sanghuangporus vaninii cultivated on cut log substrates. Front Nutr 2023; 10:1197998. [PMID: 37662599 PMCID: PMC10472941 DOI: 10.3389/fnut.2023.1197998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 06/27/2023] [Indexed: 09/05/2023] Open
Abstract
Sanghuangporus vaninii is a profitable traditional and medicinal edible fungus with uncommon therapeutic properties and medicinal value. The accumulation of active ingredients in this fungus that is used in traditional Chinese medicine is affected by its years of growth, and their pharmacological activities are also affected. However, the effects of age on the medicinal value of fruiting bodies of S. vaninii cultivated on cut log substrate remain unclear. In this study, an untargeted liquid chromatography mass spectrometry (LC-MS)-based metabolomics approach was performed to characterize the profiles of metabolites from 1-, 2- and 3-year-old fruiting bodies of S. vaninii. A total of, 156 differentially accumulated metabolites (DAMs) were screened based on the criterion of a variable importance projection greater than 1.0 and p < 0.01, including 75% up regulated and 25% down regulated. The results of enrichment of metabolic pathways showed that the metabolites involved the biosynthesis of plant secondary metabolites, biosynthesis of amino acids, central carbon metabolism in cancer, steroid hormone biosynthesis, linoleic acid metabolism, prolactin signaling pathway, and arginine biosynthesis, and so on. The biosynthesis of plant secondary metabolites pathway was significantly activated. Five metabolites were significantly elevated within the growth of fruiting bodies, including 15-keto-prostaglandin F2a, (4S, 5R)-4,5,6-trihydroxy-2-iminohexanoate, adenylsuccinic acid, piplartine, and chenodeoxycholic acid. 15-keto-prostaglandin F2a is related to the pathway of arachidonic acid metabolism and was significantly increased up to 1,320- and 535-fold in the 2- and 3-year-old fruiting bodies, respectively, compared with those in the 1-year-old group. The presence of these bioactive natural products in S. vaninii is consistent with the traditional use of Sanghuang, which prompted an exploration of its use as a source of natural prostaglandin in the form of foods and nutraceuticals. These findings may provide insight into the functional components of S. vaninii to develop therapeutic strategies.
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Affiliation(s)
- Congtao Xu
- Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Shuang Zhao
- Institute of Agri-Food Processing and Nutrition, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China
| | - Zihao Li
- Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Jinlong Pan
- Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yuanyuan Zhou
- Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Qingxiu Hu
- Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yajie Zou
- Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing, China
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Liu S, Wei W, Wang J, Chen T. Theranostic applications of selenium nanomedicines against lung cancer. J Nanobiotechnology 2023; 21:96. [PMID: 36935493 PMCID: PMC10026460 DOI: 10.1186/s12951-023-01825-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 02/18/2023] [Indexed: 03/21/2023] Open
Abstract
The incidence and mortality rates of lung cancer are among the highest in the world. Traditional treatment methods include surgery, chemotherapy, and radiotherapy. Although rapid progress has been achieved in the past decade, treatment limitations remain. It is therefore imperative to identify safer and more effective therapeutic methods, and research is currently being conducted to identify more efficient and less harmful drugs. In recent years, the discovery of antitumor drugs based on the essential trace element selenium (Se) has provided good prospects for lung cancer treatments. In particular, compared to inorganic Se (Inorg-Se) and organic Se (Org-Se), Se nanomedicine (Se nanoparticles; SeNPs) shows much higher bioavailability and antioxidant activity and lower toxicity. SeNPs can also be used as a drug delivery carrier to better regulate protein and DNA biosynthesis and protein kinase C activity, thus playing a role in inhibiting cancer cell proliferation. SeNPs can also effectively activate antigen-presenting cells to stimulate cell immunity, exert regulatory effects on innate and regulatory immunity, and enhance lung cancer immunotherapy. This review summarizes the application of Se-based species and materials in lung cancer diagnosis, including fluorescence, MR, CT, photoacoustic imaging and other diagnostic methods, as well as treatments, including direct killing, radiosensitization, chemotherapeutic sensitization, photothermodynamics, and enhanced immunotherapy. In addition, the application prospects and challenges of Se-based drugs in lung cancer are examined, as well as their forecasted future clinical applications and sustainable development.
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Affiliation(s)
- Shaowei Liu
- Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Weifeng Wei
- Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jinlin Wang
- Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
| | - Tianfeng Chen
- College of Chemistry and Materials Science, Guangdong Provincial Key Laboratory of Functional Supramolecular Coordination Materials and Applications, Jinan University, Guangzhou, 510632, China.
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5
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Sravani AB, Ghate V, Lewis S. Human papillomavirus infection, cervical cancer and the less explored role of trace elements. Biol Trace Elem Res 2023; 201:1026-1050. [PMID: 35467267 PMCID: PMC9898429 DOI: 10.1007/s12011-022-03226-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 03/29/2022] [Indexed: 02/06/2023]
Abstract
Cervical cancer is an aggressive type of cancer affecting women worldwide. Many affected individuals rely on smear tests for the diagnosis, surgery, chemotherapy, or radiation for their treatment. However, due to a broad set of undesired results and side-effects associated with the existing protocols, the search for better diagnostic and therapeutic interventions is a never-ending pursuit. In the purview, the bio-concentration of trace elements (copper, selenium, zinc, iron, arsenic, manganese, and cadmium) is seen to fluctuate during the occurrence of cervical cancer and its progression from pre-cancerous to metastatic nature. Thus, during the occurrence of cervical cancer, the detection of trace elements and their supplementation will prove to be highly advantageous in developing diagnostic tools and therapeutics, respectively. This review provides a detailed overview of cervical cancer, its encouragement by human papillomavirus infections, the mechanism of pathology, and resistance. Majorly, the review emphasizes the less explored role of trace elements, their contribution to the growth and inhibition of cervical cancer. Numerous clinical trials have been listed, thereby providing a comprehensive reference to the exploration of trace elements in the management of cervical cancer.
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Affiliation(s)
- Anne Boyina Sravani
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India
| | - Vivek Ghate
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India
| | - Shaila Lewis
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India.
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6
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Choi JA, Lee EH, Cho H, Kim JH. High-Dose Selenium Induces Ferroptotic Cell Death in Ovarian Cancer. Int J Mol Sci 2023; 24:ijms24031918. [PMID: 36768241 PMCID: PMC9915545 DOI: 10.3390/ijms24031918] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/06/2023] [Accepted: 01/11/2023] [Indexed: 01/21/2023] Open
Abstract
Selenium is a promising multi-target chemotherapeutic agent with controversial clinical results. Hence, reassessing the anticancer effects of Se is necessary to clearly understand the potential of high-dose selenium in cancer treatment. Here, we observed that high-dose sodium selenite (SS) significantly decreased the proliferation and increased the death of ovarian cancer cells, mediated by an increased generation of reactive oxygen species. Notably, high-dose SS decreased the levels of glutathione peroxidase (GPx), a selenoprotein with antioxidant properties, without altering other selenoproteins. Furthermore, high-dose SS triggered lipid peroxidation and ferroptosis, a type of iron-dependent cell death, due to dysregulated GPx4 pathways. We demonstrated that intravenous high-dose SS significantly reduced the tumor growth and weight in SKOV3-bearing mice. Consistent with our in vitro results, mice with SKOV3 cells treated with high-dose SS showed decreased GPx4 expression in tumors. Therefore, we highlight the significance of high-dose SS as a potential chemotherapeutic agent for ovarian cancer. High-dose SS-mediated ferroptotic therapy integrating glutathione depletion and ROS generation is a promising strategy for cancer therapy.
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Zhang Q, Qiang L, Liu Y, Fan M, Si X, Zheng P. Biomaterial-assisted tumor therapy: A brief review of hydroxyapatite nanoparticles and its composites used in bone tumors therapy. Front Bioeng Biotechnol 2023; 11:1167474. [PMID: 37091350 PMCID: PMC10119417 DOI: 10.3389/fbioe.2023.1167474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 03/24/2023] [Indexed: 04/25/2023] Open
Abstract
Malignant bone tumors can inflict significant damage to affected bones, leaving patients to contend with issues like residual tumor cells, bone defects, and bacterial infections post-surgery. However, hydroxyapatite nanoparticles (nHAp), the principal inorganic constituent of natural bone, possess numerous advantages such as high biocompatibility, bone conduction ability, and a large surface area. Moreover, nHAp's nanoscale particle size enables it to impede the growth of various tumor cells via diverse pathways. This article presents a comprehensive review of relevant literature spanning the past 2 decades concerning nHAp and bone tumors. The primary goal is to explore the mechanisms responsible for nHAp's ability to hinder tumor initiation and progression, as well as to investigate the potential of integrating other drugs and components for bone tumor diagnosis and treatment. Lastly, the article discusses future prospects for the development of hydroxyapatite materials as a promising modality for tumor therapy.
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Affiliation(s)
- Quan Zhang
- Department of Orthopaedic Surgery, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang, China
| | - Lei Qiang
- Department of Orthopaedic Surgery, Children’s Hospital of Nanjing Medical University, Nanjing, China
- School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, China
| | - Yihao Liu
- Department of Orthopaedic Surgery, Children’s Hospital of Nanjing Medical University, Nanjing, China
- Shanghai Key Laboratory of Orthopedic Implant, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Minjie Fan
- Department of Orthopaedic Surgery, Children’s Hospital of Nanjing Medical University, Nanjing, China
| | - Xinxin Si
- Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-industry Technology, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang, China
- *Correspondence: Xinxin Si, ; Pengfei Zheng,
| | - Pengfei Zheng
- Department of Orthopaedic Surgery, Children’s Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Xinxin Si, ; Pengfei Zheng,
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Ehudin MA, Golla U, Trivedi D, Potlakayala SD, Rudrabhatla SV, Desai D, Dovat S, Claxton D, Sharma A. Therapeutic Benefits of Selenium in Hematological Malignancies. Int J Mol Sci 2022; 23:ijms23147972. [PMID: 35887320 PMCID: PMC9323677 DOI: 10.3390/ijms23147972] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 07/09/2022] [Accepted: 07/12/2022] [Indexed: 12/14/2022] Open
Abstract
Supplementing chemotherapy and radiotherapy with selenium has been shown to have benefits against various cancers. This approach has also been shown to alleviate the side effects associated with standard cancer therapies and improve the quality of life in patients. In addition, selenium levels in patients have been correlated with various cancers and have served as a diagnostic marker to track the efficiency of treatments or to determine whether these selenium levels cause or are a result of the disease. This concise review presents a survey of the selenium-based literature, with a focus on hematological malignancies, to demonstrate the significant impact of selenium in different cancers. The anti-cancer mechanisms and signaling pathways regulated by selenium, which impart its efficacious properties, are discussed. An outlook into the relationship between selenium and cancer is highlighted to guide future cancer therapy development.
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Affiliation(s)
- Melanie A. Ehudin
- Division of Hematology and Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.A.E.); (S.D.)
| | - Upendarrao Golla
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Devnah Trivedi
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Shobha D. Potlakayala
- Department of Biological Sciences, School of Science Engineering and Technology, Penn State Harrisburg, Middletown, PA 17057, USA; (S.D.P.); (S.V.R.)
| | - Sairam V. Rudrabhatla
- Department of Biological Sciences, School of Science Engineering and Technology, Penn State Harrisburg, Middletown, PA 17057, USA; (S.D.P.); (S.V.R.)
| | - Dhimant Desai
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Sinisa Dovat
- Division of Hematology and Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (M.A.E.); (S.D.)
| | - David Claxton
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
| | - Arati Sharma
- Division of Hematology and Oncology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (U.G.); (D.C.)
- Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; (D.T.); (D.D.)
- Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
- Correspondence:
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Potential Role of Selenium in the Treatment of Cancer and Viral Infections. Int J Mol Sci 2022; 23:ijms23042215. [PMID: 35216330 PMCID: PMC8879146 DOI: 10.3390/ijms23042215] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/15/2022] [Accepted: 02/15/2022] [Indexed: 01/08/2023] Open
Abstract
Selenium has been extensively evaluated clinically as a chemopreventive agent with variable results depending on the type and dose of selenium used. Selenium species are now being therapeutically evaluated as modulators of drug responses rather than as directly cytotoxic agents. In addition, recent data suggest an association between selenium base-line levels in blood and survival of patients with COVID-19. The major focus of this mini review was to summarize: the pathways of selenium metabolism; the results of selenium-based chemopreventive clinical trials; the potential for using selenium metabolites as therapeutic modulators of drug responses in cancer (clear-cell renal-cell carcinoma (ccRCC) in particular); and selenium usage alone or in combination with vaccines in the treatment of patients with COVID-19. Critical therapeutic targets and the potential role of different selenium species, doses, and schedules were discussed.
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10
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Ohkoshi A, Ishii R, Wakamori S, Nakayama Y, Yoshida T, Higashi K, Nakanome A, Ogawa T, Katori Y. Serum selenium predicts achievement of full-dose cisplatin in concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma: A prospective, observational study. Oral Oncol 2021; 121:105475. [PMID: 34364132 DOI: 10.1016/j.oraloncology.2021.105475] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/27/2021] [Accepted: 07/28/2021] [Indexed: 11/13/2022]
Abstract
OBJECTIVE Concurrent chemoradiotherapy (CCRT) with three-weekly high-dose cisplatin (100 mg/m2) is a standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC), but compliance with cisplatin is often poor due to various adverse events. The aim of this prospective, observational study was to determine the predictors of achievement of full-dose cisplatin. METHODS A prospective, observational study was conducted involving 60 patients who received CCRT with three-weekly high-dose cisplatin (100 mg/m2) for locally advanced HNSCC. Possible predictors affecting compliance with cisplatin were subjected to univariate and multivariate logistic regression analyses. Age, sex, primary site, clinical stage, treatment intent, history of hypertension, diabetes mellitus, smoking and drinking habits, body mass index, creatinine clearance, serum albumin, controlling nutrition status, trace elements (Fe, Zn, Cu, Se), acute kidney injury, white blood cell count decrease, neutrophilia, and weight loss were the variables evaluated. RESULTS Twenty-seven patients achieved full-dose cisplatin (300 mg/m2), and the other 33 patients did not. Multivariate logistic regression analysis showed that both mild renal dysfunction and selenium deficiency before treatment independently had negative impacts on achievement of full-dose cisplatin. CONCLUSIONS As well as renal function, selenium deficiency is a potential therapeutic target for CCRT with high-dose cisplatin in HNSCC patients.
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Affiliation(s)
- Akira Ohkoshi
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan.
| | - Ryo Ishii
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
| | - Shun Wakamori
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
| | - Yuki Nakayama
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
| | - Takuya Yoshida
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
| | - Kenjiro Higashi
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
| | - Ayako Nakanome
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
| | - Takenori Ogawa
- Department of Otolaryngology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu City 501-1193, Japan
| | - Yukio Katori
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan
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11
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Barbanente A, Nadar RA, Esposti LD, Palazzo B, Iafisco M, van den Beucken JJJP, Leeuwenburgh SCG, Margiotta N. Platinum-loaded, selenium-doped hydroxyapatite nanoparticles selectively reduce proliferation of prostate and breast cancer cells co-cultured in the presence of stem cells. J Mater Chem B 2021; 8:2792-2804. [PMID: 32159578 DOI: 10.1039/d0tb00390e] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Chemotherapeutic treatment of patients with bone tumors or bone metastases often leads to severe side effects such as high drug toxicity, lack of tumor specificity and induced drug resistance. A novel strategy to treat early stages of bone metastases involves local co-delivery of multiple chemotherapeutic agents to synergistically improve the curative effect and overcome shortcomings of traditional chemotherapy. Herein we show that selenite-doped hydroxyapatite nanoparticles loaded with a hydroxyapatite-binding anti-tumor platinum complex (PtPP-HASe) selectively reduce proliferation of cancer cells without reducing proliferation of bone marrow stem cells. These PtPP-HASe particles were nanocrystalline with selenium (Se) and platinum (Pt) contents ranging between 0-10 and 1.5-3 wt%, respectively. Release kinetics of Se and Pt from PtPP-HASe nanoparticles resulted in a cumulative release of ∼10 and ∼66 wt% after 7 days, respectively. At a Pt/Se ratio of 8, released Pt and Se species selectively reduced cell number of human prostate (PC3) and human breast cancer cells (MDA-MB-231) by a factor of >10 with limited effects on co-cultured human bone marrow stem cells (hBMSc). These novel nanoparticles demonstrate high anti-cancer selectivity, which offers ample opportunities for the design of novel biomaterials with potent and selective chemotherapeutic efficacy against cancer cells.
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Affiliation(s)
- Alessandra Barbanente
- Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy.
| | - Robin A Nadar
- Department of Dentistry - Regenerative Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Philips van Leydenlaan 25, 6525 EX Nijmegen, The Netherlands
| | - Lorenzo Degli Esposti
- Institute of Science and Technology for Ceramics (ISTEC), National Research Council (CNR), Via Granarolo 64, 48018 Faenza, Italy
| | - Barbara Palazzo
- Ghimas S.p.A., c/o Distretto Tecnologico High Tech Scarl, Campus Ecotekne, Via per Monteroni, 73100 Lecce, Italy
| | - Michele Iafisco
- Institute of Science and Technology for Ceramics (ISTEC), National Research Council (CNR), Via Granarolo 64, 48018 Faenza, Italy
| | - Jeroen J J P van den Beucken
- Department of Dentistry - Regenerative Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Philips van Leydenlaan 25, 6525 EX Nijmegen, The Netherlands
| | - Sander C G Leeuwenburgh
- Department of Dentistry - Regenerative Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Philips van Leydenlaan 25, 6525 EX Nijmegen, The Netherlands and Institute of Science and Technology for Ceramics (ISTEC), National Research Council (CNR), Via Granarolo 64, 48018 Faenza, Italy
| | - Nicola Margiotta
- Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy.
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12
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Gray A, Dang BN, Moore TB, Clemens R, Pressman P. A review of nutrition and dietary interventions in oncology. SAGE Open Med 2020; 8:2050312120926877. [PMID: 32537159 PMCID: PMC7268120 DOI: 10.1177/2050312120926877] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Accepted: 04/22/2020] [Indexed: 12/11/2022] Open
Abstract
The complex cellular mechanisms and inter-related pathways of cancer proliferation, evasion, and metastasis remain an emerging field of research. Over the last several decades, nutritional research has prominent role in identifying emerging adjuvant therapies in our fight against cancer. Nutritional and dietary interventions are being explored to improve the morbidity and mortality for cancer patients worldwide. In this review, we examine several dietary interventions and their proposed mechanisms against cancer as well as identifying limitations in the currently available literature. This review provides a comprehensive review of the cancer metabolism, dietary interventions used during cancer treatment, anti metabolic drugs, and their impact on nutritional deficiencies along with a critical review of the following diets: caloric restriction, intermittent fasting, ketogenic diet, Mediterranean diet, Japanese diet, and vegan diet.
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Affiliation(s)
- Ashley Gray
- Division of Pediatric Hematology/Oncology, Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Brian N Dang
- David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Theodore B Moore
- Division of Pediatric Hematology/Oncology, Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Roger Clemens
- Pharmacology & Pharmaceutical Sciences, USC School of Pharmacy, International Center for Regulatory Science, Los Angeles, CA, USA
| | - Peter Pressman
- Polyscience Consulting & Director of Nutrition and Public Health, The Daedalus Foundation, San Clemente, CA, USA
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13
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Bai K, Hong B, He J, Huang W. Antioxidant Capacity and Hepatoprotective Role of Chitosan-Stabilized Selenium Nanoparticles in Concanavalin A-Induced Liver Injury in Mice. Nutrients 2020; 12:nu12030857. [PMID: 32210138 PMCID: PMC7146609 DOI: 10.3390/nu12030857] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 03/17/2020] [Accepted: 03/20/2020] [Indexed: 12/28/2022] Open
Abstract
Selenium nanoparticles (SeNPs) have attracted wide attention for their use in nutritional supplements and nanomedicine applications. However, their potential to protect against autoimmune hepatitis has not been fully investigated, and the role of their antioxidant capacity in hepatoprotection is uncertain. In this study, chitosan-stabilized SeNPs (CS-SeNPs) were prepared by means of rapid ultra-filtration, and then their antioxidant ability and free-radical scavenging capacity were evaluated. The hepatoprotective potential of a spray-dried CS-SeNPs powder against autoimmune liver disease was also studied in the concanavalin A (Con A)-induced liver injury mouse model. CS-SeNPs with size of around 60 nm exhibited acceptable oxygen radical absorbance capacity and were able to scavenge DPPH, superoxide anion, and hydroxyl radicals. The CS-SeNPs powder alleviated Con A-caused hepatocyte necrosis and reduced the elevated levels of serum alanine transaminase, aspartate transaminase, and lactic dehydrogenase in Con A-treated mice. These results suggest that the CS-SeNPs powder protected the mice from Con-A-induced oxidative stress in the liver by retarding lipid oxidation and by boosting the activities of superoxide dismutase, glutathione peroxidase, and catalase, partly because of its ability to improve Se retention. In conclusion, SeNPs present potent hepatoprotective potential against Con A-induced liver damage by enhancing the redox state in the liver; therefore, they deserve further development.
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Affiliation(s)
- Kaikai Bai
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (B.H.); (J.H.); (W.H.)
- Technology Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
- Correspondence: ; Tel.: +86-592-2195309
| | - Bihong Hong
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (B.H.); (J.H.); (W.H.)
- Technology Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
| | - Jianlin He
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (B.H.); (J.H.); (W.H.)
- Technology Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
| | - Wenwen Huang
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; (B.H.); (J.H.); (W.H.)
- Technology Innovation Center for Exploitation of Marine Biological Resources, Ministry of Natural Resources, Xiamen 361005, China
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14
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Hamroun A, Lenain R, Bigna JJ, Speyer E, Bui L, Chamley P, Pottier N, Cauffiez C, Dewaeles E, Dhalluin X, Scherpereel A, Hazzan M, Maanaoui M, Glowacki F. Prevention of Cisplatin-Induced Acute Kidney Injury: A Systematic Review and Meta-Analysis. Drugs 2020; 79:1567-1582. [PMID: 31429065 DOI: 10.1007/s40265-019-01182-1] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
PURPOSE Cisplatin-induced acute kidney injury (CIA) is a serious adverse event that affects 20-40% of exposed patients, despite any implemented precaution to avoid it. The aim of this work was therefore to identify a relevant nephroprotective method for CIA. METHODS We searched Pubmed, Embase, and Web of Science from 1 January 1978 to 1 June 2018, without language restriction. All studies (observational and interventional) assessing a CIA prevention method for adults receiving at least one course of cisplatin were eligible. The primary outcome was acute nephrotoxicity, as defined by the AKI-KDIGO classification (2012). The odds ratio and corresponding 95% confidence interval were used to assess the associations. We used narrative synthesis in case of heterogeneity regarding intervention, population, or outcome. When possible, a random-effects model was used to pool studies. The heterogeneity between studies was quantified (I2), and multiple meta-regressions were carried out to identify potential confounders. RESULTS Within 4520 eligible studies, 51 articles fulfilling the selection criteria were included in the review, assessing 21 different prevention methods. A meta-analysis could only be performed on the 15 observational studies concerning magnesium supplementation (1841 patients), and showed a significant nephroprotective effect for all combined grades of CIA (OR 0.24, [0.19-0.32], I2 = 0.0%). This significant nephroprotective effect was also observed for grades 2 and 3 CIA (OR 0.22, [0.14-0.33], I2 = 0.0% and OR 0.25, [0.08-0.76], I2 = 0.0%, respectively). CONCLUSION While no method of prevention had so far demonstrated its indisputable efficacy, our results highlight the potential protective effect of magnesium supplementation on cisplatin-induced acute nephrotoxicity. TRIAL REGISTRATION This study is registered in PROSPERO, CRD42018090612.
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Affiliation(s)
- Aghilès Hamroun
- Nephrology Department, CHRU Lille, University of Lille, 59000, Lille, France.
| | - Rémi Lenain
- Nephrology Department, CHRU Lille, University of Lille, 59000, Lille, France
| | - Jean Joel Bigna
- Faculty of Medicine, University of Paris Saclay, Paris, France
| | - Elodie Speyer
- Centre for Research in Epidemiology and Population Health (CESP), Paris Saclay University, Paris Sud University, Versailles Saint Quentin University, INSERM UMRS 1018, 94807, Villejuif, France
| | - Linh Bui
- Nephrology Department, CH Beuvry, Béthune, France
| | - Paul Chamley
- Nephrology Department, CHRU Lille, University of Lille, 59000, Lille, France
| | - Nicolas Pottier
- Department of Toxicology and Genetic Pathologies, CHRU Lille, 59000, Lille, France
| | - Christelle Cauffiez
- EA 4483-IMPECS-IMPact of Environmental ChemicalS on Human Health, Medicine Faculty, Research Department, University of Lille, 59045, Lille, France
| | - Edmone Dewaeles
- EA 4483-IMPECS-IMPact of Environmental ChemicalS on Human Health, Medicine Faculty, Research Department, University of Lille, 59045, Lille, France
| | - Xavier Dhalluin
- Pulmonary and Thoracic Oncology Department, University of Lille, INSERM U1189 OncoThAI, 59000, Lille, France
| | - Arnaud Scherpereel
- Pulmonary and Thoracic Oncology Department, University of Lille, INSERM U1189 OncoThAI, 59000, Lille, France
| | - Marc Hazzan
- Nephrology Department, CHRU Lille, University of Lille, 59000, Lille, France
- INSERM, UMR995, 59000, Lille, France
| | - Mehdi Maanaoui
- Nephrology Department, CHRU Lille, University of Lille, 59000, Lille, France
| | - François Glowacki
- Nephrology Department, CHRU Lille, University of Lille, 59000, Lille, France
- EA 4483-IMPECS-IMPact of Environmental ChemicalS on Human Health, Medicine Faculty, Research Department, University of Lille, 59045, Lille, France
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15
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Farhood B, Mortezaee K, Motevaseli E, Mirtavoos-Mahyari H, Shabeeb D, Eleojo Musa A, Sanikhani NS, Najafi M, Ahmadi A. Selenium as an adjuvant for modification of radiation response. J Cell Biochem 2019; 120:18559-18571. [PMID: 31190419 DOI: 10.1002/jcb.29171] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Revised: 05/20/2019] [Accepted: 05/23/2019] [Indexed: 01/06/2023]
Abstract
Ionizing radiation plays a central role in several medical and industrial purposes. In spite of the beneficial effects of ionizing radiation, there are some concerns related to accidental exposure that could pose a threat to the lives of exposed people. This issue is also very critical for triage of injured people in a possible terror event or nuclear disaster. The most common side effects of ionizing radiation are experienced in cancer patients who had undergone radiotherapy. For complete eradication of tumors, there is a need for high doses of ionizing radiation. However, these high doses lead to severe toxicities in adjacent organs. Management of normal tissue toxicity may be achieved via modulation of radiation responses in both normal and malignant cells. It has been suggested that treatment of patients with some adjuvant agents may be useful for amelioration of radiation toxicity or sensitization of tumor cells. However, there are always some concerns for possible severe toxicities and protection of tumor cells, which in turn affect radiotherapy outcomes. Selenium is a trace element in the body that has shown potent antioxidant and radioprotective effects for many years. Selenium can potently stimulate antioxidant defense of cells, especially via upregulation of glutathione (GSH) level and glutathione peroxidase activity. Some studies in recent years have shown that selenium is able to mitigate radiation toxicity when administered after exposure. These studies suggest that selenium may be a useful radiomitigator for an accidental radiation event. Molecular and cellular studies have revealed that selenium protects different normal cells against radiation, while it may sensitize tumor cells. These differential effects of selenium have also been revealed in some clinical studies. In the present study, we aimed to review the radiomitigative and radioprotective effects of selenium on normal cells/tissues, as well as its radiosensitive effect on cancer cells.
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Affiliation(s)
- Bagher Farhood
- Department of Medical Physics and Radiology, Faculty of Paramedical Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Keywan Mortezaee
- Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Elahe Motevaseli
- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hanifeh Mirtavoos-Mahyari
- Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Dheyauldeen Shabeeb
- Department of Physiology, College of Medicine, University of Misan, Misan, Iraq
| | - Ahmed Eleojo Musa
- Department of Medical Physics, Tehran University of Medical Sciences, Tehran, Iran
| | - Nafiseh Sadat Sanikhani
- Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Amirhossein Ahmadi
- Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
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16
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Muecke R, Waldschock K, Schomburg L, Micke O, Buentzel J, Kisters K, Adamietz IA, Huebner J. Whole Blood Selenium Levels and Selenium Supplementation in Patients Treated in a Family Doctor Practice in Golßen (State of Brandenburg, Germany): A Laboratory Study. Integr Cancer Ther 2018; 17:1132-1136. [PMID: 30354843 PMCID: PMC6247545 DOI: 10.1177/1534735418807971] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Introduction: The supply of selenium (Se) varies widely in Germany. Therefore, a laboratory study was conducted in patients treated at a family doctor practice in Brandenburg, Germany, to determine whether there is a general Se deficiency in this area; specifically, whether Se concentrations differ with age, sex, or presence of cancer. Moreover, we tested the effects of a Se supplementation on whole blood Se levels (WBSL). Methods: In 2006, WBSL were analyzed in 871 patients (496 females, 375 males, median age: 67 years). Of these, 143 (78 females, 65 males) had cancer and were in an aftercare situation. From 2006 to 2012, 317 patients (76 with tumors, 241 without tumors) received continuous Se supplementation with sodium selenite (300 µg per day) and annual WBSL measurements. WBSL were compared by Student’s t test for paired and independent samples. Results: The initial WBSL of all patients was 97.2 ± 20.7 µg/L (mean ± SD). WBSL did not differ with regard to age or sex, but patients with cancer had the lowest WBSL. Se supplementation increased mean WBSL in both patients with (to 128.5 µg/L) and without (to 119.52 µg/L) cancer (P < .001). Discussion: Patients with cancer displayed significantly lower WBSL than patients without cancer, indicating a negative effect of tumors on Se uptake, absorption, or metabolism. Significant influences of age or sex were not observed. Selenite supplementation efficiently improved WBSL to concentrations considered necessary for health benefits.
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Affiliation(s)
- Ralph Muecke
- 1 Radiotherapy RheinMainNahe, Bad Kreuznach, Germany.,2 Marien Hospital, Herne, Germany.,3 Ruhr University Bochum, Bochum, Germany
| | | | - Lutz Schomburg
- 5 Institute for Experimental Endocrinology, Charité, Berlin, Germany
| | | | | | | | - Irenaeus A Adamietz
- 2 Marien Hospital, Herne, Germany.,3 Ruhr University Bochum, Bochum, Germany
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Lobb RJ, Jacobson GM, Cursons RT, Jameson MB. The Interaction of Selenium with Chemotherapy and Radiation on Normal and Malignant Human Mononuclear Blood Cells. Int J Mol Sci 2018; 19:ijms19103167. [PMID: 30326581 PMCID: PMC6214079 DOI: 10.3390/ijms19103167] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 10/02/2018] [Accepted: 10/11/2018] [Indexed: 01/17/2023] Open
Abstract
Selenium, a trace element with anticancer properties, can reduce harmful toxicities of chemotherapy and radiotherapy without compromising efficacy. However, the dose-response relationship in normal versus malignant human cells is unclear. We evaluated how methylseleninic acid (MSA) modulates the toxicity and efficacy of chemotherapy and radiation on malignant and non-malignant human mononuclear blood cells in vitro. We specifically investigated its effects on endoplasmic reticulum stress induction, intracellular glutathione concentration, DNA damage and viability of peripheral blood mononuclear cells and THP1 monocytic leukaemia cells in response to radiation, cytosine arabinoside or doxorubicin chemotherapy. MSA, at lower concentrations, induced protective responses in normal cells but cytotoxic effects in malignant cells, alone and in conjunction with chemotherapy or radiation. However, in normal cells higher concentrations of MSA were directly toxic and increased the cytotoxicity of radiation but not chemotherapy. In malignant cells higher MSA concentrations were generally more effective in combination with cancer treatments. Thus, optimal MSA concentrations differed between normal and malignant cells and treatments. This work supports clinical reports that selenium can significantly reduce dose-limiting toxicities of anticancer therapies and potentially improve efficacy of anticancer treatments. The optimal selenium compound and dose is not yet determined.
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Affiliation(s)
- Richard J Lobb
- Tumour Microenvironment Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
| | - Gregory M Jacobson
- Department of Biological Sciences, University of Waikato, Hamilton 3216, New Zealand.
| | - Ray T Cursons
- Department of Biological Sciences, University of Waikato, Hamilton 3216, New Zealand.
| | - Michael B Jameson
- Oncology Department, Waikato Hospital, Hamilton 3204, New Zealand.
- Waikato Clinical Campus, Faculty of Medical and Health Sciences, University of Auckland, Hamilton 3204, New Zealand.
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18
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Song M, Kumaran MN, Gounder M, Gibbon DG, Nieves-Neira W, Vaidya A, Hellmann M, Kane MP, Buckley B, Shih W, Caffrey PB, Frenkel GD, Rodriguez-Rodriguez L. Phase I trial of selenium plus chemotherapy in gynecologic cancers. Gynecol Oncol 2018; 150:478-486. [PMID: 30068487 DOI: 10.1016/j.ygyno.2018.07.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 06/27/2018] [Accepted: 07/01/2018] [Indexed: 10/28/2022]
Abstract
PURPOSE Preclinical studies performed in our laboratory have shown that high-dose selenium inhibits the development of carboplatin drug resistance in an ovarian cancer mouse xenograft model. Based on these data, as well as the potential serious toxicities of supranutritional doses of selenium, a phase I trial of a combination of selenium/carboplatin/paclitaxel was designed to determine the maximum tolerated dose, safety, and effects of selenium on carboplatin pharmacokinetics in the treatment of chemo-naive women with gynecologic cancers. Correlative studies were performed to identify gene targets of selenium. METHODS Chemo-naïve patients with gynecologic malignancy received selenious acid IV on day 1 followed by carboplatin IV and paclitaxel IV on day 3. A standard 3 + 3 dose-escalating design was used for addition of selenium to standard dose chemotherapy. Concentrations of selenium in plasma and carboplatin in plasma ultrafiltrate were analyzed. RESULTS Forty-five patients were enrolled and 291 treatment cycles were administered. Selenium was administered as selenious acid to 9 cohorts of patients with selenium doses ranging from 50 μg to 5000 μg. Grade 3/4 toxicities included neutropenia (66.7%), febrile neutropenia (2.2%), pain (20.0%), infection (13.3%), neurologic (11.1%), and pulmonary adverse effects (11.1%). The maximum tolerated dose of selenium was not reached. Selenium had no effect on carboplatin pharmacokinetics. Correlative studies showed post-treatment downregulation of RAD51AP1, a protein involved in DNA repair, in both cancer cell lines and patient tumors. CONCLUSION Overall, the addition of selenium to carboplatin/paclitaxel chemotherapy is safe and well tolerated, and does not alter carboplatin pharmacokinetics. A 5000 μg dose of elemental selenium as selenious acid is suggested as the dose to be evaluated in a phase II trial.
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Affiliation(s)
- Mihae Song
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Muthu N Kumaran
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Murugesan Gounder
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Darlene G Gibbon
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Wilberto Nieves-Neira
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Ami Vaidya
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Mira Hellmann
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Michael P Kane
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Brian Buckley
- Rutgers Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Road, Piscataway, NJ 08854, United States
| | - Weichung Shih
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States
| | - Paula B Caffrey
- Department of Biological Sciences, Rutgers University, 195 University Avenue, Newark, NJ 07102, United States; Department of Biological and Environmental Sciences, 250 University Avenue, California University of PA, California, PA 15419, United States
| | - Gerald D Frenkel
- Department of Biological Sciences, Rutgers University, 195 University Avenue, Newark, NJ 07102, United States
| | - Lorna Rodriguez-Rodriguez
- Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, United States; Rutgers-Robert Wood Johnson Medical School, Department of Obstetrics, Gynecology and Reproductive Sciences, 125 Paterson Street, New Brunswick, NJ 08901, United States.
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19
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Selenium in Radiation Oncology-15 Years of Experiences in Germany. Nutrients 2018; 10:nu10040483. [PMID: 29652817 PMCID: PMC5946268 DOI: 10.3390/nu10040483] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 04/05/2018] [Accepted: 04/11/2018] [Indexed: 11/17/2022] Open
Abstract
Introduction: Se measurement and supplementation in radiation oncology is a controversial issue. The German Working Group Trace Elements and Electrolytes in Oncology (AKTE) has conducted a number of studies on this issue, which are summarized in this review. Strategies have been tested and developed, aiming to stratify the patients with a potential need for supplemental Se and how best to monitor Se supplementation with respect to health effects and risks. Methods: We analyzed blood and tissue Se-levels of different tumor patients (n = 512). Two randomized phase III clinical studies were conducted for testing a potential radioprotective effect of supplemental Se during radiation therapy in patients with uterine cancer (n = 81) and head and neck tumor patients (n = 39). Results: A relative Se deficit in whole blood or serum was detected in the majority of tumor patients (carcinomas of the uterus, head and neck, lung, rectal or prostate cancer). In prostate cancer, tissue Se concentrations were relatively elevated in the carcinoma centre as compared to the surrounding compartment or as compared to tumor samples from patients with benign prostatic hyperplasia. Adjuvant Se supplementation successfully corrected Se-deficiency in the patients analyzed and decreased radiotherapy-induced diarrhea in a randomized study of radiotherapy patients with carcinomas of the uterus. Survival data imply that Se supplementation did not interfere with radiation success. Some positive effects of supplemental Se in the prevention of ageusia (loss of taste) and dysphagia due to radiotherapy were noted in a second randomized trial in patients with head and neck cancer. We have not observed any adverse effects of supplemental Se in our studies. Conclusions: Se supplementation yielded promising results concerning radioprotection in tumor patients and should be considered as a promising adjuvant treatment option in subjects with a relative Se deficit.
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Zakharia Y, Bhattacharya A, Rustum YM. Selenium targets resistance biomarkers enhancing efficacy while reducing toxicity of anti-cancer drugs: preclinical and clinical development. Oncotarget 2018; 9:10765-10783. [PMID: 29535842 PMCID: PMC5828194 DOI: 10.18632/oncotarget.24297] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 01/13/2018] [Indexed: 12/31/2022] Open
Abstract
Selenium (Se)-containing molecules exert antioxidant properties and modulate targets associated with tumor growth, metastasis, angiogenesis, and drug resistance. Prevention clinical trials with low-dose supplementation of different types of Se molecules have yielded conflicting results. Utilizing several xenograft models, we earlier reported that the enhanced antitumor activity of various chemotherapeutic agents by selenomethione and Se-methylselenocysteine in several human tumor xenografts is highly dose- and schedule-dependent. Further, Se pretreament offered selective protection of normal tissues from drug-induced toxicity, thereby allowing higher dosing than maximum tolerated doses. These enhanced therapeutic effects were associated with inhibition of hypoxia-inducible factor 1- and 2-alpha (HIF1α, HIF2α) protein, nuclear factor (erythyroid-derived 2)-like 2 (Nrf2) and pair-related homeobox-1 (Prx1) transcription factors, downregulation of oncogenic- and upregulation of tumor suppressor miRNAs. This review provides: 1) a brief update of clinical prevention trials with Se; 2) advances in the use of specific types, doses, and schedules of Se that selectively modulate antitumor activity and toxicity of anti-cancer drugs; 3) identification of targets selectively modulated by Se; 4) plasma and tumor tissue Se levels achieved after oral administration of Se in xenograft models and cancer patients; 5) development of a phase 1 clinical trial with escalating doses of orally administered selenomethionine in sequential combination with axitinib to patients with advanced clear cell renal cell carcinoma; and 6) clinical prospects for future therapeutic use of Se in combination with anticancer drugs.
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Affiliation(s)
- Yousef Zakharia
- University of Iowa Division of Medical Oncology and Hematology, Holden Comprehensive Cancer Center, Iowa City, IA, USA
| | - Arup Bhattacharya
- Roswell Park Cancer Institute, Department of Pharmacology and Therapeutics, Buffalo, NY, USA
| | - Youcef M. Rustum
- University of Iowa Division of Medical Oncology and Hematology, Holden Comprehensive Cancer Center, Iowa City, IA, USA
- Roswell Park Cancer Institute, Department of Pharmacology and Therapeutics, Buffalo, NY, USA
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21
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Ouyang Y, Peng Y, Li J, Holmgren A, Lu J. Modulation of thiol-dependent redox system by metal ionsviathioredoxin and glutaredoxin systems. Metallomics 2018; 10:218-228. [DOI: 10.1039/c7mt00327g] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Metal and metalloid ions regulate thioredoxin and glutaredoxin system-mediated biological functions by targeting mammalian thioredoxin reductase and mitochondrial glutaredoxin 2&5.
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Affiliation(s)
- Yanfang Ouyang
- Key Laboratory of Luminescent and Real-Time Analytical Chemistry
- Ministry of Education
- College of Pharmaceutical Sciences
- Southwest University
- Chongqing 400715
| | - Yi Peng
- Key Laboratory of Luminescent and Real-Time Analytical Chemistry
- Ministry of Education
- College of Pharmaceutical Sciences
- Southwest University
- Chongqing 400715
| | - Jing Li
- Key Laboratory of Luminescent and Real-Time Analytical Chemistry
- Ministry of Education
- College of Pharmaceutical Sciences
- Southwest University
- Chongqing 400715
| | - Arne Holmgren
- Division of Biochemistry
- Department of Medical Biochemistry and Biophysics
- Karolinska Institutet
- SE-171 77 Stockholm
- Sweden
| | - Jun Lu
- Key Laboratory of Luminescent and Real-Time Analytical Chemistry
- Ministry of Education
- College of Pharmaceutical Sciences
- Southwest University
- Chongqing 400715
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Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity - Exploring the armoury of obscurity. Saudi Pharm J 2017; 26:177-190. [PMID: 30166914 PMCID: PMC6111235 DOI: 10.1016/j.jsps.2017.12.013] [Citation(s) in RCA: 149] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Accepted: 12/14/2017] [Indexed: 12/14/2022] Open
Abstract
Cancer is the leading cause of mortality worldwide, accounting for almost 13% of deaths in the world. Among the conventional cancer treatments, chemotherapy is most frequently carried out to treat malignant cancer rather than localised lesions which is amenable to surgery and radiotherapy. However, anticancer drugs are associated with a plethora of side effects. Each drug, within every class, has its own set of adverse reactions which may cause patient incompliance and deterioration of the quality of life. One of the major causes of adverse reactions, especially for drugs targeting DNA, is the excessive production of reactive oxygen species (ROS) and subsequent build up of oxidative stress. To curb these undesired side effects, several dietary supplements have been tested, amongst which antioxidants have gained increasing popularity as adjuvant in chemotherapy. However, many oncologists discourage the use of antioxidant rich food supplements because these may interfere with the modalities which kill cancer by generating free radicals. In the present review, all studies reporting concomitant use of several antioxidants with chemotherapy are indiscriminately included and discussed impartially. The effect of supplementation of thirteen different antioxidants and their analogues as a single agent or in combination with chemotherapy has been compiled in this article. The present review encompasses a total of 174 peer-reviewed original articles from 1967 till date comprising 93 clinical trials with a cumulative number of 18,208 patients, 56 animal studies and 35 in vitro studies. Our comprehensive data suggests that antioxidant has superior potential of ameliorating chemotherapeutic induced toxicity. Antioxidant supplementation during chemotherapy also promises higher therapeutic efficiency and increased survival times in patients.
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Chen H, Busse LW. Novel Therapies for Acute Kidney Injury. Kidney Int Rep 2017; 2:785-799. [PMID: 29270486 PMCID: PMC5733745 DOI: 10.1016/j.ekir.2017.06.020] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Revised: 06/17/2017] [Accepted: 06/19/2017] [Indexed: 12/25/2022] Open
Abstract
Acute kidney injury (AKI) is a common disease with a complex pathophysiology. The old paradigm of identifying renal injury based on location-prerenal, intrarenal, and postrenal-is now being supplanted with a new paradigm based on observable kidney injury patterns. The pathophysiology of AKI on a molecular and microanatomical level includes inflammation, immune dysregulation, oxidative injury, and impaired microcirculation. Treatment has traditionally been supportive, including the avoidance of nephrotoxins, judicious volume and blood pressure management, hemodynamic monitoring, and renal replacement therapy. Fluid overload and chloride-rich fluids are now implicated in the development of AKI, and resuscitation with a balanced, buffered solution at a conservative rate will mitigate risk. Novel therapies, which address specific observable kidney injury patterns include direct oxygen-free radical scavengers such as α-lipoic acid, curcumin, sodium-2-mercaptoethane sulphonate, propofol, and selenium. In addition, angiotensin II and adenosine receptor antagonists hope to ameliorate kidney injury via manipulation of renal hemodynamics and tubulo-glomerular feedback. Alkaline phosphatase, sphingosine 1 phosphate analogues, and dipeptidylpeptidase-4 inhibitors counteract kidney injury via manipulation of inflammatory pathways. Finally, genetic modifiers such as 5INP may mitigate AKI via transcriptive processes.
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Affiliation(s)
- Huaizhen Chen
- Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Laurence William Busse
- Department of Medicine, Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
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Wang J, Seebacher N, Shi H, Kan Q, Duan Z. Novel strategies to prevent the development of multidrug resistance (MDR) in cancer. Oncotarget 2017; 8:84559-84571. [PMID: 29137448 PMCID: PMC5663620 DOI: 10.18632/oncotarget.19187] [Citation(s) in RCA: 141] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Accepted: 06/26/2017] [Indexed: 12/16/2022] Open
Abstract
The development of multidrug resistance (MDR) is one of the major challenges to the success of traditional chemotherapy treatment in cancer patients. Most studies to date have focused on strategies to reverse MDR following its development. However, agents utilizing this approach have proven to be of limited clinical use, failing to demonstrate an improvement in therapeutic efficacy with almost no significant survival benefits observed in cancer clinical trials. An alternative approach that has been applied is to prevent or delay MDR prior or early in its development. Recent investigations have shown that preventing the emergence of MDR at the onset of chemotherapy treatment, rather than reversing MDR once it has developed, may assist in overcoming drug resistance. In this review, we focus on a number of novel strategies used by small-molecule inhibitors to prevent the development of MDR. These agents hold great promise for prolonging the efficacy of chemotherapy treatment and improving the clinical outcomes of patients with cancers that are susceptible to MDR development.
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Affiliation(s)
- Jinglu Wang
- Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People's Republic of China.,Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Nicole Seebacher
- Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Huirong Shi
- Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People's Republic of China
| | - Quancheng Kan
- Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People's Republic of China
| | - Zhenfeng Duan
- Department of Gynecologic Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People's Republic of China.,Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
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25
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Ling N, Zhou X, Ji Y, Li W, Ji C, Qi Z. Immuno-modulatory and cellular antioxidant activities of κ-selenocarrageenan in combination with Epirubicin in H22 hepatoma-bearing mice. Biomed Pharmacother 2017; 91:132-137. [PMID: 28448867 DOI: 10.1016/j.biopha.2017.04.064] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 03/15/2017] [Accepted: 04/13/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The aim of this study is to evaluate the synergistic anti-tumor effects and underlying mechanism of κ-selenocarrageenan (KSC) in combination with the chemotherapy drug epirubicin (EPI) in H22 tumor-bearing mice. METHODS Hepatocellular carcinoma H22 cells were implanted into mice. After the transplants were successfully established, the animals were divided into four groups: namely the control group, the KSC group, the EPI group and the KSC+EPI group. The effects of KSC and EPI on tumor growth, survival time, thymus index, spleen index, white blood cells (WBC), splenocyte proliferation, natural killer (NK) cell activity, serum TNF-α and IL-2 levels, and antioxidant enzymes in the liver cells were determined. RESULTS KSC and/or EPI significantly reduced tumor weight and prolonged the survival time. Furthermore, KSC could attenuate EPI-induced atrophy in the thymus and spleen, as well as other toxicities, which may indicate an additive effect of this combination against organ dysfunction and cellular injury. KSC significantly promoted Con A- and LPS-stimulated splenocyte proliferation, enhanced NK cell activity, and reversed the inhibition of NK activity induced by EPI (P<0.01). In addition, KSC could elevate serum TNF-α and IL-2 levels, increase the GSH-Px, SOD, CAT and GSH activity levels in liver tissue, and reduce MDA content. CONCLUSIONS These results suggest that KSC can regulate immune function in mice and suppress the growth of tumor in H22 tumor-bearing mice, and its synergistic antitumor activity with epirubicin may be related to its antioxidant and immuno-modulatory effects.
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Affiliation(s)
- Na Ling
- College of Science, Harbin University of Commerce, Harbin 150076, Heilongjiang Province, China.
| | - Xiaojun Zhou
- College of Life Science, Luoyang Normal University, Luoyang 471022, Henan Province, China.
| | - Yubin Ji
- College of Science, Harbin University of Commerce, Harbin 150076, Heilongjiang Province, China
| | - Wenlan Li
- College of Science, Harbin University of Commerce, Harbin 150076, Heilongjiang Province, China
| | - Chenfeng Ji
- College of Science, Harbin University of Commerce, Harbin 150076, Heilongjiang Province, China
| | - Zheng Qi
- College of Science, Harbin University of Commerce, Harbin 150076, Heilongjiang Province, China
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Nematbakhsh M, Pezeshki Z, Eshraghi Jazi F, Mazaheri B, Moeini M, Safari T, Azarkish F, Moslemi F, Maleki M, Rezaei A, Saberi S, Dehghani A, Malek M, Mansouri A, Ghasemi M, Zeinali F, Zamani Z, Navidi M, Jilanchi S, Shirdavani S, Ashrafi F. Cisplatin-Induced Nephrotoxicity; Protective Supplements and Gender Differences. Asian Pac J Cancer Prev 2017; 18:295-314. [PMID: 28345324 PMCID: PMC5454720 DOI: 10.22034/apjcp.2017.18.2.295] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Cisplatin (CDDP) has been widely used as a chemotherapeutic agent for solid tumors. The most common side effect of CDDP is nephrotoxicity, and many efforts have been made in the laboratory and the clinic to employ candidate adjuvants to CDDP to minimize this adverse influence. Many synthetic and herbal antioxidants as well as trace elements have been investigated for this purpose in recent years and a variety of positive and negative results have been yielded. However, no definitive supplement has so far been proposed to prevent CDDP-induced nephrotoxicity; however, this condition is gender related and the sex hormone estrogen may protect the kidney against CDDP damage. In this review, the results of research related to the effect of different synthetic and herbal antioxidants supplements are presented and discussed with suggestions included for future work.
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Affiliation(s)
- Mehdi Nematbakhsh
- Water and Electrolytes Research Center, Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran. *
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El-Badry AEMA, Khalifa MM. Geochemical Assessments and Distribution of Arsenic, Selenium, Tin and Antimony in the Surfacial Bottom Sediments of Brullus Lagoon and its Effects on Human Health. ECOLOGIA 2016; 7:20-28. [DOI: 10.3923/ecologia.2017.20.28] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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28
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Gröber U, Holzhauer P, Kisters K, Holick MF, Adamietz IA. Micronutrients in Oncological Intervention. Nutrients 2016; 8:163. [PMID: 26985904 PMCID: PMC4808891 DOI: 10.3390/nu8030163] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 02/16/2016] [Accepted: 02/24/2016] [Indexed: 12/14/2022] Open
Abstract
Nutritional supplements are widely used among patients with cancer who perceive them to be anticancer and antitoxicity agents. Depending on the type of malignancy and the gender 30%-90% of the cancer patients supplement their diets with antioxidant and immuno-stabilizing micronutrients, such as selenium, vitamin C, and vitamin D, often without the knowledge of the treating physician. From the oncological viewpoint, there are justifiable concerns that dietary supplements decrease the effectiveness of chemotherapy and radiotherapy. Recent studies, however, have provided increasing evidence that treatment is tolerated better-with an increase in patient compliance and a lower rate of treatment discontinuations-when micronutrients, such as selenium, are added as appropriate to the patient's medication. Nutritional supplementation tailored to an individual's background diet, genetics, tumor histology, and treatments may yield benefits in subsets of patients. Clinicians should have an open dialogue with patients about nutritional supplements. Supplement advice needs to be individualized and come from a credible source, and it is best communicated by the physician.
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Affiliation(s)
- Uwe Gröber
- Akademie für Mikronährstoffmedizin, Essen, Zweigertstrasse 55, 45130 Essen, Germany.
| | - Peter Holzhauer
- Akademie für Mikronährstoffmedizin, Essen, Zweigertstrasse 55, 45130 Essen, Germany.
- Interdisziplinäres onkologisches Zentrum (IOZ), München, Nußbaumstrasse 12, München 80336, Germany.
- Klinik Bad Trissl, Innere Medizin II-Onkologie und Komplementärmedizin, Oberaudorf 83080, Germany.
| | - Klaus Kisters
- Akademie für Mikronährstoffmedizin, Essen, Zweigertstrasse 55, 45130 Essen, Germany.
- St. Anna Hospital, Medizinische Klinik I, Herne, Hospitalstrasse 19, Herne 44649, Germany.
| | - Michael F Holick
- Boston University Medical Center, 85 East Newton Street M-1033, Boston, MA 02118, USA.
| | - Irenäus A Adamietz
- Klinik für Strahlentherapie und Radio-Onkologie, Ruhr Universität Bochum (RUB), Hölkeskampring 40, Herne 44625, Germany.
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Yasueda A, Urushima H, Ito T. Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment: A Systematic Review. Integr Cancer Ther 2016; 15:17-39. [PMID: 26503419 PMCID: PMC5736082 DOI: 10.1177/1534735415610427] [Citation(s) in RCA: 103] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Oxidative stress is a key component in carcinogenesis. Although radiation produces reactive oxygen species, some anticancer agents such as alkylating agents, platinum and antitumor antibiotics exert cytotoxicity by generating free radicals. Nonenzymatic exogenous antioxidants such as vitamins, minerals, and polyphenols can quench ROS activity. However, whether antioxidants alter antitumor effects during radiotherapy and some types of chemotherapy remains unclear. In the present study, we reviewed antioxidants as an adjuvant therapy for cancer patients during chemotherapy or radiotherapy. Electronic literature searches were performed to select all randomized controlled clinical trials (RCTs) in which antioxidants were administered to cancer patients along with chemotherapy or radiotherapy. Articles or abstracts written in English were included. In total, 399 reports received primary screening. Duplicated articles and those meeting the exclusion criteria (not RCT, not human, and no oral administration) were excluded. Finally, 49 reports matching the inclusion criteria were included. It was difficult to determine whether antioxidants affect treatment outcomes or whether antioxidants ameliorate adverse effects induced by chemotherapy and radiotherapy. It is desirable to use an evidence-based method to select supplements best suited to cancer patients. Although there are many opinions about risks or benefits of antioxidant supplementation, we could mostly conclude that the harm caused by antioxidant supplementation remains unclear for patients during cancer therapy, except for smokers undergoing radiotherapy.
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Affiliation(s)
- Asuka Yasueda
- Osaka University Graduate School of Medicine, Suita City, Japan
| | - Hayato Urushima
- Osaka University Graduate School of Medicine, Suita City, Japan
| | - Toshinori Ito
- Osaka University Graduate School of Medicine, Suita City, Japan
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30
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Mix M, Ramnath N, Gomez J, Groot CD, Rajan S, Dibaj S, Tan W, Rustum Y, Jameson MB, Singh AK. Effects of selenomethionine on acute toxicities from concurrent chemoradiation for inoperable stage III non-small cell lung cancer. World J Clin Oncol 2015; 6:156-165. [PMID: 26468452 PMCID: PMC4600190 DOI: 10.5306/wjco.v6.i5.156] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 06/06/2015] [Accepted: 06/18/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To prospectively determine the safety and tolerability of oral L-selenomethionine (SLM) with concurrent chemoradiation (CCRT) for Stage III non-small cell lung cancer (NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use. METHODS Sixteen patients with stage III NSCLC were accrued to this single arm, phase II study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly IV paclitaxel 50 mg/m(2) followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment. RESULTS No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients (19%), pneumonitis in 0, leukopenia in 2 (12.5%), and anemia in 1 (6%); the latter two were significantly reduced when compared to the protocol-stated expected rate of 35% (P = 0.045 for leukopenia, and P < 0.01 for anemia). Median overall survival was 14.9 mo and median failure-free survival was 9 mo (95%CI: 3.3-21.5). CONCLUSION There may be some protective benefit of selenium in the setting of CCRT for inoperable NSCLC. The data suggests decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted.
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Huo S, Dong J, Shen S, Ren Y, Song C, Xu J, Shi T. L-selenomethionine reduces platinum(IV) anticancer model compounds at strikingly faster rates than L-methionine. Dalton Trans 2015; 43:15328-36. [PMID: 25075569 DOI: 10.1039/c4dt01528b] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
L-Selenomethionine (SeMet), the predominant form of selenium acquired from the diet by humans, has been used as a supplement, and exhibit some important functions like cancer prevention and antioxidative defense. Its interactions with Pt(II) anticancer drugs have been characterized, but its redox reactions with platinum(IV) anticancer prodrugs have not been exploited. In this work, the oxidation of SeMet by Pt(IV) anticancer model compounds trans-[PtX2(CN)4](2-) (X = Cl, Br) was characterized. A stopped-flow spectrometer was used to record the rapid scan spectra and to follow the reaction kinetics over a wide pH range. An overall second-order rate law was derived: -d[Pt(IV)]/dt = k'[Pt(IV)][SeMet], where k' pertains to the observed second-order rate constants. The k'-pH profiles showed that k' increased only about 6 times even though the solution pH was varied from 0.25 to 10.5. The redox stoichiometry was determined as Δ[Pt(IV)]/Δ[SeMet] = 1 : (1.07 ± 0.07), suggesting that SeMet was oxidized to selenomethionine selenoxide. The selenoxide together with its hydrated form was identified explicitly by high resolution mass spectral analysis. A reaction mechanism was proposed which encompassed three parallel rate-determining steps relying on the protolytic species of SeMet. Rate constants of the rate-determining steps were obtained from the simulations of the k'-pH profiles. Activation parameters were determined for the reactions of the zwitterionic form of SeMet with the Pt(IV) complexes. A bridged electron transfer process is delineated in the rate-determining steps and several lines of evidence support the bridged electron transfer mode. Strikingly, reduction of [PtX2(CN)4](2-) by SeMet is 3.7 × 10(3)-5.7 × 10(4) times faster than that by L-methionine. Some potential biological consequences resulting from the strikingly fast reduction are discussed.
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Affiliation(s)
- Shuying Huo
- College of Chemistry and Environmental Science, and the MOE Key Laboratory of Medicinal Chemistry and Molecular Diagnostics, Hebei University, Baoding 071002, Hebei Province, P. R. China.
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Misra S, Boylan M, Selvam A, Spallholz JE, Björnstedt M. Redox-active selenium compounds--from toxicity and cell death to cancer treatment. Nutrients 2015; 7:3536-56. [PMID: 25984742 PMCID: PMC4446766 DOI: 10.3390/nu7053536] [Citation(s) in RCA: 216] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Revised: 04/24/2015] [Accepted: 05/05/2015] [Indexed: 11/29/2022] Open
Abstract
Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed.
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Affiliation(s)
- Sougat Misra
- Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.
| | - Mallory Boylan
- Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, P.O. Box 41270, Lubbock, TX 79409-1270, USA.
| | - Arun Selvam
- Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.
| | - Julian E Spallholz
- Department of Nutritional Sciences, College of Human Sciences, Texas Tech University, P.O. Box 41270, Lubbock, TX 79409-1270, USA.
| | - Mikael Björnstedt
- Division of Pathology F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.
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Shukla P, Singh R. Potential pharmacological interventions against hematotoxicity: an overview. Expert Rev Hematol 2015; 8:505-14. [PMID: 25843128 DOI: 10.1586/17474086.2015.1031106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Various treatment regimens, including chemotherapy, are known to induce heavy oxidative stress on the system, which in turn leads to adverse effects on healthy tissues. Blood being prone to oxidative stress is affected the most. At this juncture, it might not be prudent to anticipate having chemotherapeutic agents with no hematotoxicity; the best way forward is to look for potential anti-hematotoxic compounds, which could be supplemented to exposed patients, thus reducing the toxic burden on blood cells. We mined existing literature for reviewing possible interventions against hematotoxicity and figured that there is a great lacuna in this field in terms of not having such useful information at one place. This review presents the possible entities based on their antioxidant potentials, including their mechanistic pathways.
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Affiliation(s)
- Pooja Shukla
- Academy for Scientific and Innovative Research, New Delhi 110 001, India
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Ji YB, Ling N, Zhou XJ, Mao YX, Li WL, Chen N. Schedule-dependent effects of kappa-selenocarrageenan in combination with epirubicin on hepatocellular carcinoma. Asian Pac J Cancer Prev 2015; 15:3651-7. [PMID: 24870773 DOI: 10.7314/apjcp.2014.15.8.3651] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Hepatocellular carcinoma (HCC) has a relatively higher incidence in many countries of Asia. Globally, HCC has a high fatality rate and short survival. Epirubicin, a doxorubicin analogue, may be administered alone or in combination with other agents to treat primary liver cancer and metastatic diseases. However, the toxic effects of epirubicin to normal tissues and cells have been one of the major obstacles to successful cancer chemotherapy. Here, we investigated the effects of epirubicin in combination with kappa-selenocarrageenan on mice with H22 implanted tumors and HepG-2 cell proliferation, immune organ index, morphology, cell cycle and related protein expressions in vivo and in vitro with sequential drug exposure. The inhibitory rate of tumor growth in vivo was calculated. Drug sensitivity was measured by MTT assay, and the King's principle was used to evaluate the interaction of drug combination. Morphological changes were observed by fluorescent microscopy. Cell cycle changes were analyzed by flow cytometry. Expression of cyclin A, Cdc25A and Cdk2 were detected by Western blotting. In vivo results demonstrated that the inhibitory rate of EPI combined with KSC was higher than that of KSC or EPI alone, and the Q value indicated an additive effect. In addition, KSC could significantly raise the thymus and spleen indices of mice with H22 implanted tumors. In the drug sensitivity assay in vitro, exposure to KSC and EPI simultaneously was more effective than exposure sequentially in HepG-2 cells, while exposure to KSC prior to EPI was more effective than exposure to EPI prior to KSC. Q values showed an additive effect in the simultaneous group and antagonistic effects in the sequential groups. Morphological analysis showed similar results to the drug sensitivity assay. Cell cycle analysis revealed that exposure to KSC or EPI alone arrested the cells in S phase in HepG-2 cells, exposure to KSC and EPI simultaneously caused accumulation in the S phase, an effect caused by either KSC or EPI. Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. Taken together, our findings suggest that KSC in combination with EPI might have potential as a new therapeutic regimen against HCC.
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Affiliation(s)
- Yu-Bin Ji
- Life Science and Environmental Science Research Center, Harbin University of Commerce, Harbin, China E-mail :
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Muecke R, Micke O, Schomburg L, Buentzel J, Adamietz IA, Huebner J. Serum selenium deficiency in patients with hematological malignancies: is a supplementation study mandatory? Acta Haematol 2014; 132:256-8. [PMID: 24903215 DOI: 10.1159/000360903] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Accepted: 02/26/2014] [Indexed: 11/19/2022]
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Panchuk R, Skorokhyd N, Chumak V, Lehka L, Omelyanchik S, Gurinovich V, Moiseenok A, Heffeter P, Berger W, Stoika R. Specific antioxidant compounds differentially modulate cytotoxic activity of doxorubicin and cisplatin: in vitro and in vivo study. Croat Med J 2014; 55:206-17. [PMID: 24891279 PMCID: PMC4049213 DOI: 10.3325/cmj.2014.55.206] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Aim To use the antioxidant compounds (sodium selenite, selenomethionine, D-pantethine) for modulation of cytotoxic effect of doxorubicin and cisplatin toward wild type and drug-resistant mutants of several human tumor cells. Similar treatments were applied in vivo toward adult male Wistar rats. Methods Human tumor cells of different lines (HCT-116, Jurkat and HL-60) with various mechanisms of drug-resistance were treated with doxorubicin or cisplatin, alone or in combination with sodium selenite, selenomethionine, or D-pantethine. Cell viability, induction of apoptosis, and production of O2- radicals were measured. Activity of redox potential modulating enzymes was measured in the liver and blood plasma of adult male Wistar rats subjected to similar treatments. Results All antioxidants used in physiologically harmless concentration inhibited cytotoxic action of doxorubicin toward tumor cells sensitive to chemotherapy treatment by 15%-30%, and slightly enhanced cytotoxic effect of this medicine toward drug-resistant malignant cells. At the same time, there was no significant effect of these antioxidants on cisplatin action. Such effects were accompanied by a complete inhibition of production of superoxide radicals induced by doxorubicin. The results of in vivo study in adult male Wistar rats were in agreement with the results of in vitro study of human tumor cells. Conclusion Protective effect of specific antioxidant agents during cytotoxic action of doxorubicin was demonstrated in vitro in drug-sensitive human tumor cells and in adult male Wistar rats, while there was no protective effect in drug-resistant sub-lines of these tumor cells during action of doxorubicin and cisplatin.
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Affiliation(s)
- Rostyslav Panchuk
- Rostyslav Panchuk, Institute of Cell Biology, National Academy of Sciences of Ukraine, Drahomanov Street 14/16, 79005, Lviv, Ukraine,
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Se-methylselenocysteine offers selective protection against toxicity and potentiates the antitumour activity of anticancer drugs in preclinical animal models. Br J Cancer 2014; 110:1733-43. [PMID: 24619073 PMCID: PMC3974093 DOI: 10.1038/bjc.2014.85] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 12/18/2013] [Accepted: 01/09/2014] [Indexed: 02/06/2023] Open
Abstract
Background: Identification and development of drugs that can effectively modulate the therapeutic efficacy and toxicity of chemotherapy remain an unmet challenge. We evaluated the effects of Se-methylselenocysteine (MSC) on the toxicity and antitumour activity of cyclophosphamide, cisplatin, oxaliplatin, and irinotecan in animal models. Methods: Cyclophosphamide, cisplatin, and oxaliplatin were administered by a single i.v. injection and irinotecan by i.v. weekly × 4 schedules. For the combination, MSC was administered daily via the oral route for 7 days in mice and daily for 14 days in rats before and concurrent with drug administration. Results: Se-methylselenocysteine significantly protected against organ-specific toxicity induced by lethal doses of cyclophosphamide, cisplatin, oxaliplatin, and irinotecan. These include diarrhoea, stomatitis, alopecia, bladder, kidney, and bone marrow toxicities. Protection from lethal toxicity by MSC was associated with enhanced antitumour activity in rats bearing advanced Ward colorectal carcinoma and in nude mice bearing human squamous cell carcinoma of the head and neck, FaDu, and A253 xenografts. Conclusions: Se-methylselenocysteine offers selective protection against organ-specific toxicity induced by clinically active agents and enhances further antitumour activity, resulting in improved therapeutic index. These data provided the rationale for the need to clinically evaluate MSC as selective modulator of the antitumour activity and selectivity of anticancer drugs.
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Rjiba-Touati K, Ayed-Boussema I, Soualeh N, Achour A, Bacha H, Abid S. Antioxidant and antigenotoxic role of recombinant human erythropoeitin against alkylating agents: Cisplatin and mitomycin C in cultured Vero cells. Exp Biol Med (Maywood) 2013; 238:943-50. [DOI: 10.1177/1535370213494643] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Cisplatin (CDDP) and mitomycin C (MMC), two alkylating agents used against various solid tumours, are a common source of acute kidney injury. Thus, strategies for minimizing CDDP and MMC toxicity are of a clinical interest. In this study, we aimed to investigate the protective role of recombinant human erythropoietin (rhEPO) against oxidative stress and genotoxicity induced by CDDP and MMC in cultured Vero cells. Three types of treatments were performed: (i) cells were treated with rhEPO 24 h before exposure to CDDP/MMC (pre-treatment), (ii) cells were treated with rhEPO and CDDP/MMC simultaneously (co-treatment), (iii) cells were treated with rhEPO 24 h after exposure to CDDP/MMC (post-treatment). Our results showed that rhEPO decreased the reactive oxygen species levels, the malondialdehyde levels and ameliorated glutathione (reduced and oxidized glutathione) modulation induced by CDDP and MMC in cultured Vero cells. Furthermore, rhEPO administration prevented alkylating agents-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, against CDDP- and MMC-induced oxidative stress and genotoxicity, especially in pre-treatment condition.
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Affiliation(s)
- Karima Rjiba-Touati
- Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir University, 5019 Monastir, Tunisia
| | - Imen Ayed-Boussema
- Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir University, 5019 Monastir, Tunisia
| | - Nidhal Soualeh
- Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir University, 5019 Monastir, Tunisia
| | - Abdellatif Achour
- Department of Nephrology, Dialysis and Transplant, University Hospital of Sahloul, 4021 Sousse, Tunisia
| | - Hassen Bacha
- Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir University, 5019 Monastir, Tunisia
| | - Salwa Abid
- Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir University, 5019 Monastir, Tunisia
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Ghorbani A, Omidvar B, Parsi A. Protective effect of selenium on cisplatin induced nephrotoxicity: A double-blind controlled randomized clinical trial. J Nephropathol 2013; 2:129-34. [PMID: 24475439 DOI: 10.12860/jnp.2013.21] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2012] [Revised: 12/28/2012] [Accepted: 01/15/2013] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Renal injury is common following cisplatin infusion. Some agents have been used to attenuate cisplatin nephrotoxicity. However, except hydration, none of them has been proved to be effective. OBJECTIVE In this study selenium as an antioxidant supplement was tested on cisplatin induced renal injury. PATIENTS AND METHODS 122 cancerous patients (85 male and 37 female; age range of 14 to 82 years old) were enrolled to receive chemotherapy regimens consisting cisplatin. They were allocated into two groups using a random number list . Investigators, patients and analyzers all, were blinded in allocation by using sealed opaque envelopes. Intervention group received a single 400 mcg selenium tablet and patients in control group took a placebo tablet which was similar with selenium preparation in color, weight, shape and taste. Primary end points were an increase in plasma creatinine above 1.5 mg/dl in men and 1.4mg/dl in women, or increase of plasma creatinine more than 50% from baseline or urine flow rate less than 0.5 ml/kg/h. Creatinine level was measured initially and on the 5th day after cisplatin therapy. RESULTS There was no difference in cumulative dose of cisplatin between the groups (p=0.54). There were not evidences of acute renal failure (ARF) in cases. While, among placebo group, 7 patients had criteria of acute kidney injury. Conclusions :selenium could probably prevent cisplatin-induced acute kidney injury, when it is added to hydration therapy in cancerous patients.
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Affiliation(s)
- Ali Ghorbani
- Department of Nephrology, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Bita Omidvar
- Department of Rheumatology, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Abazar Parsi
- Department of Internal Medicine, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Protective effect of selenium on cisplatin induced nephrotoxicity: A double-blind controlled randomized clinical trial. J Nephropathol 2013. [DOI: 10.5812/nephropathol.10656] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Gröber U, Mücke R, Adamietz I, Holzhauer P, Kisters K, Büntzel J, Micke O. Komplementärer Einsatz von Antioxidanzien und Mikronährstoffen in der Onkologie. DER ONKOLOGE 2013. [DOI: 10.1007/s00761-012-2385-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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The efficacy of selenium in prevention of oral mucositis in patients undergoing hematopoietic SCT: a randomized clinical trial. Bone Marrow Transplant 2013; 48:832-6. [PMID: 23292233 DOI: 10.1038/bmt.2012.250] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Oral mucositis (OM) is a complication of high-dose chemotherapy (HDC) followed by hematopoietic SCT (HSCT) with few effective treatments. Selenium has a cytoprotective role via the glutathione peroxidase (Glu.Px) enzyme and prevents chemotherapy-induced toxicities. We performed a double-blind, randomized, placebo-controlled study to evaluate the efficacy of selenium on the prevention of OM in 77 patients with leukemia, undergoing allogeneic HSCT. Thirty-seven patients received oral selenium tablets (200 mcg twice daily) from the starting day of HDC to 14 days after transplantation. OM was evaluated daily for 21 days after transplantation according to World Health Organization oral toxicity scale. The incidence of severe OM (grades 3-4) was significantly lower in the selenium group (10.8% vs 35.1%, P<0.05). We noted that the duration of objective OM (grades 2-4), excluding patient's self-declaration (grade 1), was significantly shorter in the selenium group (3.6±1.84 vs 5.3±2.2 days, P=0.014). Significant elevations in serum selenium level and plasma Glu.Px activity were observed 7 and 14 days after transplantation compared with baseline in the selenium group. We conclude that selenium can reduce the duration and severity of OM after HDC. Clinicaltrial.org ID: NCT01432873.
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Park JS, Ryu JY, Jeon HK, Cho YJ, Park YA, Choi JJ, Lee JW, Kim BG, Bae DS. The effects of selenium on tumor growth in epithelial ovarian carcinoma. J Gynecol Oncol 2012; 23:190-6. [PMID: 22808362 PMCID: PMC3395015 DOI: 10.3802/jgo.2012.23.3.190] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2012] [Revised: 04/09/2012] [Accepted: 04/09/2012] [Indexed: 11/30/2022] Open
Abstract
Objective Epidemiological studies suggest that selenium protects against the development of several cancers. Selenium (sodium selenite) has been reported to interfere with cell growth and proliferation, and to induce cell death. In this study, we tested whether selenium could have growth-inhibiting effect in ovarian cancer cells and an orthotopic animal model. Methods Cell growth in selenium-treated cells was determined in human ovarian cancer cells, A2780, HeyA8, and SKOV3ip1 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Animal experiment of selenium with paclitaxel was performed using SKOV3ip1 cells in nude mice to evaluate their inhibiting effect for tumor growth. In addition, another animal experiment of paclitaxel with or without selenium was performed to assess the effect of survival and food intake in mice. Results The in vitro growth of selenium-treated cells was significantly decreased dose-dependently in A2780, HeyA8, and SKOV3ip1 cells. Therapy experiment in mice was started 1 week after injection of the SKOV3ip1 cells. Treatment with selenium (1.5 mg/kg, 3 times/week) and paclitaxel injection showed no addictive effect of the inhibition of tumor growth. However, combination of selenium and paclitaxel showed the slightly increased food intake compared with paclitaxel alone. Conclusion Although selenium has growth-inhibiting effect in ovarian carcinoma cells in vitro, there is no additive effect on tumor growth in mice treated with combination of paclitaxel and selenium. However, food intake is slightly higher in selenium-treated mice during chemotherapy.
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Affiliation(s)
- Jin Sun Park
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Li J, Sun K, Ni L, Wang X, Wang D, Zhang J. Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity. Toxicol Appl Pharmacol 2012; 258:376-83. [DOI: 10.1016/j.taap.2011.11.020] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2011] [Revised: 11/21/2011] [Accepted: 11/28/2011] [Indexed: 11/15/2022]
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Nakayama A, Alladin KP, Igbokwe O, White JD. Systematic review: generating evidence-based guidelines on the concurrent use of dietary antioxidants and chemotherapy or radiotherapy. Cancer Invest 2011; 29:655-67. [PMID: 22085269 PMCID: PMC3666569 DOI: 10.3109/07357907.2011.626479] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The risk-benefit ratio for concurrent use of dietary antioxidants with chemotherapy or radiation therapy is a controversial topic. In this review, the medical literature on concurrent antioxidant use with chemotherapy or radiotherapy was assessed and further steps for generating evidence-based guidelines are suggested. The clinical cancer research community should cooperate and focus new studies on the use of a specific combination of antioxidant and chemotherapy or radiotherapy, and determine optimal doses for a specific cancer setting. Mechanistic studies on the interaction between antioxidants and conventional cancer therapy could lead to novel biomarkers for assessing dose adequacy.
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Affiliation(s)
- Akiko Nakayama
- Preferred Staffing Group, Inc., Washington, District of Columbia, USA
| | - Karen P. Alladin
- Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, Bethesda, Maryland, USA
| | - Obianuju Igbokwe
- Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, Bethesda, Maryland, USA
| | - Jeffrey D. White
- Office of Cancer Complementary and Alternative Medicine, National Cancer Institute, Bethesda, Maryland, USA
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Fritz H, Kennedy D, Fergusson D, Fernandes R, Cooley K, Seely A, Sagar S, Wong R, Seely D. Selenium and lung cancer: a systematic review and meta analysis. PLoS One 2011; 6:e26259. [PMID: 22073154 PMCID: PMC3208545 DOI: 10.1371/journal.pone.0026259] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2011] [Accepted: 09/23/2011] [Indexed: 11/29/2022] Open
Abstract
Background Selenium is a natural health product widely used in the treatment and prevention of lung cancers, but large chemoprevention trials have yielded conflicting results. We conducted a systematic review of selenium for lung cancers, and assessed potential interactions with conventional therapies. Methods and Findings Two independent reviewers searched six databases from inception to March 2009 for evidence pertaining to the safety and efficacy of selenium for lung cancers. Pubmed and EMBASE were searched to October 2009 for evidence on interactions with chemo- or radiation-therapy. In the efficacy analysis there were nine reports of five RCTs and two biomarker-based studies, 29 reports of 26 observational studies, and 41 preclinical studies. Fifteen human studies, one case report, and 36 preclinical studies were included in the interactions analysis. Based on available evidence, there appears to be a different chemopreventive effect dependent on baseline selenium status, such that selenium supplementation may reduce risk of lung cancers in populations with lower baseline selenium status (serum<106 ng/mL), but increase risk of lung cancers in those with higher selenium (≥121.6 ng/mL). Pooling data from two trials yielded no impact to odds of lung cancer, OR 0.93 (95% confidence interval 0.61–1.43); other cancers that were the primary endpoints of these trials, OR 1.51 (95%CI 0.70–3.24); and all-cause-death, OR 0.93 (95%CI 0.79–1.10). In the treatment of lung cancers, selenium may reduce cisplatin-induced nephrotoxicity and side effects associated with radiation therapy. Conclusions Selenium may be effective for lung cancer prevention among individuals with lower selenium status, but at present should not be used as a general strategy for lung cancer prevention. Although promising, more evidence on the ability of selenium to reduce cisplatin and radiation therapy toxicity is required to ensure that therapeutic efficacy is maintained before any broad clinical recommendations can be made in this context.
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Affiliation(s)
- Heidi Fritz
- Department of Research and Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
| | - Deborah Kennedy
- Department of Research and Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
- Leslie Dan Faculty of Pharmacy, The University of Toronto, Toronto, Ontario, Canada
| | - Dean Fergusson
- Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Rochelle Fernandes
- Department of Research and Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
- Laboratory Medicine and Pathobiology (LMP), The University of Toronto, Toronto, Ontario, Canada
| | - Kieran Cooley
- Department of Research and Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
- Leslie Dan Faculty of Pharmacy, The University of Toronto, Toronto, Ontario, Canada
| | - Andrew Seely
- Department of Surgery, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Stephen Sagar
- Juravinski Cancer Centre and Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Raimond Wong
- Juravinski Cancer Centre and Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Dugald Seely
- Department of Research and Epidemiology, The Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
- Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- * E-mail:
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Rjiba-Touati K, Ayed-Boussema I, Belarbia A, Azzebi A, Achour A, Bacha H. Protective effect of recombinant human erythropoeitin against cisplatin cytotoxicity and genotoxicity in cultured Vero cells. ACTA ACUST UNITED AC 2011; 65:181-7. [PMID: 21924599 DOI: 10.1016/j.etp.2011.08.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2010] [Revised: 07/24/2011] [Accepted: 08/18/2011] [Indexed: 12/12/2022]
Abstract
Cisplatin is an effective agent against various solid tumors. Despite its effectiveness, the dose of cisplatin that can be administered is limited by its nephrotoxicity. Therefore, strategies for minimising the toxicity of cisplatin are of a clinical interest. The aim of this study was to investigate the protective effect of recombinant human erythropoietin (rhEPO) against the cytotoxicity and apoptosis induced by cisplatin in cultured Vero cells. Three types of treatments were performed: (i) cells were treated with rhEPO 24 h before exposure to cisplatin (pre-treatment), (ii) cells were treated with rhEPO and cisplatin simultaneously (co-treatment), (iii) cells were treated with rhEPO 24 h after exposure to cisplatin (post-treatment). Our results showed that rhEPO reduced cisplatin-induced cell mortality. Besides, rhEPO administration prevented cisplatin-induced DNA damage. Furthermore, rhEPO decreased the caspase-3 activity and pro-apoptotic factors levels (p53 and Bax) induced by cisplatin. It increased also the expression of the anti-apoptotic factor Bcl2 in Vero cells. Altogether, our results suggest a protective action of rhEPO against cisplatin cytotoxicity and genotoxicity via an anti-apoptotic process. The most protective effect was observed with rhEPO when it was administrated 24 h before cisplatin treatment.
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Affiliation(s)
- Karima Rjiba-Touati
- Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir University, Monastir, Tunisia
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Marković SD, Djačić DS, Cvetković DM, Obradović AD, Žižić JB, Ognjanović BI, Štajn AŠ. Effects of acute in vivo cisplatin and selenium treatment on hematological and oxidative stress parameters in red blood cells of rats. Biol Trace Elem Res 2011; 142:660-70. [PMID: 20680510 DOI: 10.1007/s12011-010-8788-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2010] [Accepted: 07/19/2010] [Indexed: 11/27/2022]
Abstract
Although cisplatin (cisPt) is one of the most often used cytotoxic drugs in the treatment of cancer, its clinical application is associated with nephrotoxicity and a cumulative anemia. In this study, we evaluated posible protective effects of selenium (Se) on hematological and oxidative stress parameters in rats, acutely treated with cisPt. Four groups of Wistar albino rats included control rats, cisPt-treated (7.5 mg/kg of body weight of cisPt, i.p.), Se-treated (6 mg/kg of body weight of Na(2)SeO(4), i.p.), and Se and cisPt co-treated rats. The rats were killed 72 h after treatment; hematological and oxidative stress parameters were followed in red blood cells. The results showed depletion in platelet number induced by high acute doses of cisPt and strong utilization of reduced glutathione, resulting in elevation of GSSG/2 GSH ratio. Se treatment was followed by stimulated erythropoiesis, increased lipid peroxidation, and GSH depletion. Se and cisPt co-treatment were followed by stimulated erythropoiesis and significant recovery of reduced glutathione status when compared with cisPt-treated rats. In conclusion, acute doses of Se and cisPt primarily act as pro-oxidants. CisPt influenced antioxidative properties of exogenous Se and their synergistic effects may partially participate in protection against cisPt-induced toxicity.
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Affiliation(s)
- Snežana D Marković
- Faculty of Science, Department for Biology and Ecology, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, P.O. Box 60, Serbia.
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Stevens J, Waters R, Sieniawska C, Kassam S, Montoto S, Fitzgibbon J, Rohatiner A, Lister A, Joel S. Serum selenium concentration at diagnosis and outcome in patients with haematological malignancies. Br J Haematol 2011; 154:448-56. [DOI: 10.1111/j.1365-2141.2011.08744.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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García Sar D, Montes-Bayón M, Blanco González E, Sierra Zapico LM, Sanz-Medel A. Reduction of Cisplatin-Induced Nephrotoxicity in Vivo by Selenomethionine: The Effect on Cisplatin–DNA Adducts. Chem Res Toxicol 2011; 24:896-904. [DOI: 10.1021/tx200085n] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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