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1
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Park SH, Gye MC. Dibutyl phthalate disrupts [Ca 2+] i, reactive oxygen species, [pH] i, protein kinases and mitochondrial activity, impairing sperm function. J Environ Sci (China) 2025; 151:68-78. [PMID: 39481973 DOI: 10.1016/j.jes.2024.03.015] [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: 11/24/2023] [Revised: 03/07/2024] [Accepted: 03/08/2024] [Indexed: 11/03/2024]
Abstract
To explore the mechanism of sperm dysfunction caused by dibutyl phthalate (DBP), the effects of DBP on intracellular [Ca2+] and [pH], reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) levels, phosphorylation of protein kinase A (PKA) substrate proteins and phosphotyrosine (p-Tyr) proteins, sperm motility, spontaneous acrosome reaction, and tail bending were examined in mouse spermatozoa. At 100 µg/mL, DBP significantly increased tail bending and [Ca2+]i. Interestingly, DBP showed biphasic effects on [pH]i. DBP at 10-100 µg/mL significantly decreased sperm motility. Similarly, Ca2+ ionophore A23187 decreased [pH]i sperm motility, suggesting that DBP-induced excessive [Ca2+]i decreased sperm motility. DBP significantly increased ROS and LPO. DBP at 100 µg/mL significantly decreased mPTP closing, MMP, and ATP levels in spermatozoa, as did H2O2, indicative of ROS-mediated mitochondrial dysfunction caused by DBP. DBP as well as H2O2 increased p-Tyr sperm proteins and phosphorylated PKA substrate sperm proteins. DBP at 1-10 µg/mL significantly increased the spontaneous acrosome reaction, suggesting that DBP can activate sperm capacitation. Altogether, DBP showed a biphasic effect on intracellular signaling in spermatozoa. At concentrations relevant to seminal ortho-phthalate levels, DBP activates [pH]i, protein tyrosine kinases and PKA via physiological levels of ROS generation, potentiating sperm capacitation. DBP at high doses excessively raises [Ca2+]i and ROS and disrupts [pH]i, impairing the mitochondrial function, tail structural integrity, and sperm motility.
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Affiliation(s)
- Seung Hyun Park
- Department of Life Science and Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea
| | - Myung Chan Gye
- Department of Life Science and Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea.
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2
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Wang S, Bai H, Liu T, Yang J, Wang Z. Optimization of concentrations of different n-3PUFAs on antioxidant capacity in mouse hepatocytes. Lipids Health Dis 2024; 23:214. [PMID: 38982376 PMCID: PMC11232338 DOI: 10.1186/s12944-024-02202-0] [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: 03/20/2024] [Accepted: 06/29/2024] [Indexed: 07/11/2024] Open
Abstract
Omega-3 polyunsaturated fatty acids (n-3 PUFAs), mainly including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), possess antioxidant properties and play a crucial role in growth and development. However, the combined effects of ALA, EPA, and DHA at different concentrations have rarely been reported. This work explored the effects of EPA, ALA, and DHA on the viability and antioxidant capacity of mouse hepatocytes, with the objective of enhancing the antioxidant capacity. Within the appropriate concentration range, cell viability and the activity of glutathione S-transferase, superoxide dismutase, and catalase were increased, while the oxidation products of malondialdehyde and the level of intracellular reactive oxygen species were obviously reduced. Thus, oxidative stress was relieved, and cellular antioxidant levels were improved. Finally, response surface optimization was carried out for EPA, ALA, and DHA, and the model was established. The antioxidant capacity of the cells was highest at EPA, ALA, and DHA concentrations of 145.46, 405.05, and 551.52 µM, respectively. These findings lay the foundation for further exploration of the interactive mechanisms of n-3 PUFAs in the body, as well as their applications in nutraceutical food.
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Affiliation(s)
- Shuting Wang
- Nourse Science Centre for Pet Nutrition, Wuhu, 241200, China
| | - Huasong Bai
- Nourse Science Centre for Pet Nutrition, Wuhu, 241200, China
| | - Tong Liu
- Nourse Science Centre for Pet Nutrition, Wuhu, 241200, China
| | - Jiayi Yang
- School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China
| | - Zhanzhong Wang
- Nourse Science Centre for Pet Nutrition, Wuhu, 241200, China.
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3
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Montecillo-Aguado M, Tirado-Rodriguez B, Huerta-Yepez S. The Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer. Int J Mol Sci 2023; 24:11691. [PMID: 37511450 PMCID: PMC10380946 DOI: 10.3390/ijms241411691] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 07/12/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease characterized by various hallmarks, including dysregulation in apoptotic cell death pathways. Apoptosis is a programmed cell death process that efficiently eliminates damaged cells. Several studies have indicated the involvement of polyunsaturated fatty acids (PUFAs) in apoptosis, including omega-3 PUFAs such as alpha-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid. However, the role of omega-6 PUFAs, such as linoleic acid, gamma-linolenic acid, and arachidonic acid, in apoptosis is controversial, with some studies supporting their activation of apoptosis and others suggesting inhibition. These PUFAs are essential fatty acids, and Western populations today have a high consumption rate of omega-6 to omega-3 PUFAs. This review focuses on presenting the diverse molecular mechanisms evidence in both in vitro and in vivo models, to help clarify the controversial involvement of omega-3 and omega-6 PUFAs in apoptosis mechanisms in cancer.
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Affiliation(s)
- Mayra Montecillo-Aguado
- Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez, Mexico City 06720, Mexico
- Programa de Doctorado en Ciencias Biomédicas, Facultad de Medicina, Universidad Nacional Autónoma de Mexico (UNAM), Mexico City 04510, Mexico
| | - Belen Tirado-Rodriguez
- Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez, Mexico City 06720, Mexico
| | - Sara Huerta-Yepez
- Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez, Mexico City 06720, Mexico
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4
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Gao G, Zhou J, Wang H, Ke L, Zhou J, Ding Y, Ding W, Zhang S, Rao P. Fish oil nano-emulsion kills macrophage: Ferroptosis triggered by catalase-catalysed superoxide eruption. Food Chem 2023; 408:135249. [PMID: 36566546 DOI: 10.1016/j.foodchem.2022.135249] [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: 07/12/2022] [Revised: 12/09/2022] [Accepted: 12/17/2022] [Indexed: 12/24/2022]
Abstract
Fish oil is increasingly utilised in the form of nano-emulsion as a nutrient and function fortifier. The nano-emulsions exceptionally high content of polyunsaturated fatty acids and electron donors at the oil/water interface provide an ideal site of the redox reaction. Here we report that a vigorous superoxide production in the fish oil nano-emulsion was catalysed by mammalian catalase in acellular and cellular systems. The resulting superoxide increased cytosolic reactive oxygen species (ROS) and membrane lipid peroxidation of murine macrophage, which eventually causes fatal oxidative damages. Cell death, was significantly inhibited by a catalase-specific inhibitor 3-Amino-1,2,4-triazole (3-AT), was via ferroptosis and not apoptosis. The ferroptosis was independent of free iron or glutathione peroxidase suppression. Our findings discovered a hidden health risk of the widely acclaimed fish oil emulsion, suggesting a novel cellular damage mechanism caused by dietary unsaturated fats on the alimentary tract mucosa.
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Affiliation(s)
- Guanzhen Gao
- Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Jingru Zhou
- Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Huiqin Wang
- Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Lijing Ke
- Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China.
| | - Jianwu Zhou
- Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Yanan Ding
- Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Wei Ding
- Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Suyun Zhang
- Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
| | - Pingfan Rao
- Food Nutrition Science Centre, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
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Wang H, Hao W, Yang L, Yan P, Wei S. Preconditioning with procyanidin B2 protects MAC-T cells against heat exposure-induced mitochondrial dysfunction and inflammation. Mol Immunol 2022; 147:126-135. [DOI: 10.1016/j.molimm.2022.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/29/2022] [Accepted: 05/02/2022] [Indexed: 11/25/2022]
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Zhang Y, Zhang Y, Yang Z, Fan Y, Chen M, Zhao M, Dai B, Zheng L, Zhang D. Cytotoxicity Effect of Iron Oxide (Fe3O4)/Graphene Oxide (GO) Nanosheets in Cultured HBE Cells. Front Chem 2022; 10:888033. [PMID: 35615314 PMCID: PMC9124895 DOI: 10.3389/fchem.2022.888033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 03/31/2022] [Indexed: 11/13/2022] Open
Abstract
Iron oxide (Fe3O4), a classical magnetic material, has been widely utilized in the field of biological magnetic resonance imaging Graphene oxide (GO) has also been extensively applied as a drug carrier due to its high specific surface area and other properties. Recently, numerous studies have synthesized Fe3O4/GO nanomaterials for biological diagnosis and treatments, including photothermal therapy and magnetic thermal therapy. However, the biosafety of the synthesized Fe3O4/GO nanomaterials still needs to be further identified. Therefore, this research intended to ascertain the cytotoxicity of Fe3O4/GO after treatment with different conditions in HBE cells. The results indicated the time-dependent and concentration-dependent cytotoxicity of Fe3O4/GO. Meanwhile, exposure to Fe3O4/GO nanomaterials increased reactive oxygen species (ROS) levels, calcium ions levels, and oxidative stress in mitochondria produced by these nanomaterials activated Caspase-9 and Caspase-3, ultimately leading to cell apoptosis.
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Affiliation(s)
- Yule Zhang
- Engineering Research Center of Optical Instrument and System, the Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai, China
| | - Yatian Zhang
- Medical College Jining Medical University, Jining, China
| | - Zhijin Yang
- Engineering Research Center of Optical Instrument and System, the Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai, China
| | - Yan Fan
- Engineering Research Center of Optical Instrument and System, the Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai, China
| | - Mengya Chen
- Engineering Research Center of Optical Instrument and System, the Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai, China
| | - Mantong Zhao
- Department of Physics and Electronic Engineering, Heze University, Heze, China
| | - Bo Dai
- Engineering Research Center of Optical Instrument and System, the Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai, China
| | - Lulu Zheng
- Engineering Research Center of Optical Instrument and System, the Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai, China
- *Correspondence: Lulu Zheng, ; Dawei Zhang,
| | - Dawei Zhang
- Engineering Research Center of Optical Instrument and System, the Ministry of Education, Shanghai Key Laboratory of Modern Optical System, University of Shanghai for Science and Technology, Shanghai, China
- Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai, China
- *Correspondence: Lulu Zheng, ; Dawei Zhang,
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7
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Ortega L, Lobos-González L, Reyna-Jeldes M, Cerda D, De la Fuente-Ortega E, Castro P, Bernal G, Coddou C. The Ω-3 fatty acid docosahexaenoic acid selectively induces apoptosis in tumor-derived cells and suppress tumor growth in gastric cancer. Eur J Pharmacol 2021; 896:173910. [PMID: 33508285 DOI: 10.1016/j.ejphar.2021.173910] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 01/18/2021] [Accepted: 01/21/2021] [Indexed: 11/25/2022]
Abstract
Despite current achievements and innovations in cancer treatment, conventional chemotherapy has several limitations, such as unsatisfactory long-term survival, cancer drug resistance and toxicity against non-tumoral cells. In the search for safer therapeutic alternatives, docosahexaenoic acid (DHA) has shown promising effects inhibiting tumor growth without significant side effects in several types of cancer, but in gastric cancer (GC) its effects have not been completely described. In this study, we characterized the effects of DHA in GC using in vivo and in vitro models. Among all of the evaluated Ω-3 and Ω-6 fatty acids, DHA showed the highest antiproliferative potency and selectivity against the GC-derived cell line AGS. 10-100 μM DHA decreased AGS cell viability in a concentration-dependent manner but had no effect on non-tumoral GES-1 cells. To evaluate if the effects of DHA were due to apoptosis induction, cells were stained with Annexin V-PI, observing that 75 and 100 μM DHA increased apoptosis in AGS, but not in GES-1 cells. Additionally, levels of several proapoptotic and antiapoptotic regulators were assessed by qPCR, western blot and activity assays, showing similar results. In order to evaluate DHA efficacy in vivo, xenografts in an immunodeficient mouse model (BALB/cNOD-SCID) were used. In these experiments, DHA treatment for six weeks consistently reduced subcutaneous tumor size, ascitic fluid volume and liver metastasis. In summary, we found that DHA has a selective antiproliferative effect on GC, being this effect driven by apoptosis induction. Our investigation provides promising features for DHA as potential therapeutic agent in GC.
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Affiliation(s)
- Lorena Ortega
- Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica Del Norte, Coquimbo, Chile
| | - Lorena Lobos-González
- Centro de Medicina Regenerativa, Facultad de Medicina-Clínica Alemana, Universidad Del Desarrollo, Santiago, Chile; Fundación Ciencia y Vida, Santiago, Chile
| | - Mauricio Reyna-Jeldes
- Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica Del Norte, Coquimbo, Chile; Millennium Nucleus for the Study of Pain (MiNuSPain), Chile
| | - Daniela Cerda
- Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica Del Norte, Coquimbo, Chile
| | - Erwin De la Fuente-Ortega
- Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica Del Norte, Coquimbo, Chile
| | - Patricio Castro
- Laboratory of Physiology and Pharmacology for Neural Development, LAND, Facultad de Ciencias Biológicas, Universidad de Concepción, Chile
| | - Giuliano Bernal
- Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica Del Norte, Coquimbo, Chile
| | - Claudio Coddou
- Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica Del Norte, Coquimbo, Chile; Millennium Nucleus for the Study of Pain (MiNuSPain), Chile.
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8
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Story MJ. Zinc, ω-3 polyunsaturated fatty acids and vitamin D: An essential combination for prevention and treatment of cancers. Biochimie 2020; 181:100-122. [PMID: 33307154 DOI: 10.1016/j.biochi.2020.11.019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 11/14/2020] [Accepted: 11/25/2020] [Indexed: 02/07/2023]
Abstract
Zinc, ω-3 polyunsaturated fatty acids (PUFAs) and vitamin D are essential nutrients for health, maturation and general wellbeing. Extensive literature searches have revealed the widespread similarity in molecular biological properties of zinc, ω-3 PUFAs and vitamin D, and their similar anti-cancer properties, even though they have different modes of action. These three nutrients are separately essential for good health, especially in the aged. Zinc, ω-3 PUFAs and vitamin D are inexpensive and safe as they are fundamentally natural and have the properties of correcting and inhibiting undesirable actions without disturbing the normal functions of cells or their extracellular environment. This review of the anticancer properties of zinc, ω-3 PUFAs and vitamin D is made in the context of the hallmarks of cancer. The anticancer properties of zinc, ω-3 PUFAs and vitamin D can therefore be used beneficially through combined treatment or supplementation. It is proposed that sufficiency of zinc, ω-3 PUFAs and vitamin D is a necessary requirement during chemotherapy treatment and that clinical trials can have questionable integrity if this sufficiency is not checked and maintained during efficacy trials.
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Affiliation(s)
- Michael J Story
- Story Pharmaceutics Pty Ltd, PO Box 6086, Linden Park, South Australia, 5065, Australia.
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9
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Yan Z, Zhan J, Qi W, Lin J, Huang Y, Xue X, Pan X. The Protective Effect of Luteolin in Glucocorticoid-Induced Osteonecrosis of the Femoral Head. Front Pharmacol 2020; 11:1195. [PMID: 32903480 PMCID: PMC7435053 DOI: 10.3389/fphar.2020.01195] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 07/22/2020] [Indexed: 01/22/2023] Open
Abstract
Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a frequently occurring type of nontraumatic osteonecrosis. A failure of the timely treatment can eventually result in the collapse of the subchondral bone structure. Luteolin (Lut), a compound extracted from Rhizoma Drynariae, is reported to possess multiple pharmacological properties including anticancer, antioxidant, antiapoptosis, and antiinflammatory properties. However, whether Lut has a protective effect on the development of GIONFH remains unclear. In this study, we evaluated the effect of Lut on Dexamethasone (Dex)-induced STAT1/caspase3 pathway in vitro and evaluated GIONFH model in vivo. In vitro, Lut inhibited the upregulation of Dex-induced phospho-STAT1, cleaved caspase9, and cleaved caspase3. In addition, Lut inhibited Dex-induced expression of Bax and cytochrome c and increased the expression of B cell lymphoma-2(Bcl-2). In vivo, Lut decreased the proportion of empty lacunae in rats with GIONFH. Taken together, these findings indicate that Lut may have therapeutic potential in the treatment of GIONFH. Further, this effect might be achieved by suppressing mitochondrial apoptosis of osteoblasts via inhibition of STAT1 activity.
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Affiliation(s)
- Zijian Yan
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou, China.,The Second School of Medicine, WenZhou Medical University, Wenzhou, China
| | - Jingdi Zhan
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou, China.,The Second School of Medicine, WenZhou Medical University, Wenzhou, China
| | - Weihui Qi
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.,Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou, China.,The Second School of Medicine, WenZhou Medical University, Wenzhou, China
| | - Jian Lin
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Yijiang Huang
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xinghe Xue
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiaoyun Pan
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
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10
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Tafesh-Edwards G, Eleftherianos I. JNK signaling in Drosophila immunity and homeostasis. Immunol Lett 2020; 226:7-11. [PMID: 32598968 DOI: 10.1016/j.imlet.2020.06.017] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 06/12/2020] [Accepted: 06/24/2020] [Indexed: 01/29/2023]
Abstract
As members of the mitogen-activated protein kinase (MAPK) family, the c-Jun N-terminal kinases (JNKs) regulate cell responses to a wide range of extrinsic and intrinsic insults, including irradiation, reactive oxygen species (ROS), DNA damage, heat, bacterial antigens, and inflammatory cytokines. Particularly, JNK signaling regulates and promotes many important physiological processes that influence metabolic and tissue homeostasis, cell death/survival, and cell damage repair and ultimately impacts the lifespan of an organism. This diverse functionality causes a variety of tissue-specific and context-specific cellular responses, mediated by various cross talks between JNK and other cellular signaling pathways. Thus, highlighting its significance as a determinant of stress responses, JNK loss-of-function mutations have been implicated in a multitude of pathologies, including neurodegenerative diseases, diabetes, and cancer. Because JNK functions are specified in a context-dependent manner and can greatly vary, the underlying causes for these different outcomes remain largely unresolved despite the gained knowledge of many regulatory roles of JNK signaling during the past two decades. In Drosophila melanogaster, JNK signaling is conserved and required for immune responses, as well as the development for morphogenetic processes (embryonic dorsal closure and thorax closure). Therefore, Drosophila innate immunity provides the ideal model to understand the complex mechanisms underlying JNK activation and regulation. In the following, we review studies in Drosophila that highlight several mechanisms by which JNK signaling influences immunity and homeostasis.
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Affiliation(s)
- Ghada Tafesh-Edwards
- Infection and Innate Immunity Lab, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, Science and Engineering Hall, 800 22nd Street NW, Washington DC, 20052, USA
| | - Ioannis Eleftherianos
- Infection and Innate Immunity Lab, Department of Biological Sciences, Institute for Biomedical Sciences, The George Washington University, Science and Engineering Hall, 800 22nd Street NW, Washington DC, 20052, USA.
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11
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Anti-tumor mechanism of eicosapentaenoic acid (EPA) on ovarian tumor model by improving the immunomodulatory activity in F344 rats. J Funct Foods 2020. [DOI: 10.1016/j.jff.2019.103739] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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12
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Oono K, Ohtake K, Watanabe C, Shiba S, Sekiya T, Kasono K. Contribution of Pyk2 pathway and reactive oxygen species (ROS) to the anti-cancer effects of eicosapentaenoic acid (EPA) in PC3 prostate cancer cells. Lipids Health Dis 2020; 19:15. [PMID: 32005121 PMCID: PMC6993438 DOI: 10.1186/s12944-019-1122-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 09/30/2019] [Indexed: 01/04/2023] Open
Abstract
Background n-3 polyunsaturated fatty acids (n-3 PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are thought to exert protective effects in cardiovascular diseases. In addition, n-3 PUFAs have demonstrated anti-cancer effects in vitro and in vivo. Objective We investigated the anti-cancer effects and mechanism of action of EPA on PC3 prostate cancer cells in vitro. Methods PC3 cells were treated with various concentrations of EPA, and cell survival and the abilities of migration and invasion were evaluated. The time course of the growth inhibitory effect of EPA on PC3 cells was also assessed. The mechanism underlying the anti-cancer effects of EPA was investigated by human phosphokinase and human apoptosis antibody arrays, and confirmed by western blot analysis. We also examined the contribution of reactive oxygen species (ROS) to the effects of EPA using the ROS inhibitor N-acetyl cysteine. Results EPA decreased the survival of PC3 cells in a dose-dependent manner within 3 h of application, with an effective concentration of 500 μmol/L. EPA inhibited proline-rich tyrosine kinase (Pyk)2 and extracellular signal-regulated kinase 1/2 phosphorylation as determined by western blotting and the antibody arrays. The growth of PC3 cells was inhibited by EPA, which was dependent on ROS induction, while EPA inhibited Pyk2 phosphorylation independent of ROS production. Conclusions Inhibition of Pyk2 phosphorylation and ROS production contribute to the anticancer effects of EPA on PC3 cells.
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Affiliation(s)
- Keiichi Oono
- Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
| | - Kazuo Ohtake
- Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
| | - Chie Watanabe
- Laboratory of Clinical Pathology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
| | - Sachiko Shiba
- Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
| | - Takashi Sekiya
- Laboratory of Clinical Pathology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan
| | - Keizo Kasono
- Laboratory of Physiology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
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13
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Liu Y, Su G, Wang S, Sun B, Zheng L, Zhao M. A highly absorbable peptide GLPY derived from elastin protect fibroblasts against UV damage via suppressing Ca2+ influx and ameliorating the loss of collagen and elastin. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.103487] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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14
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Nie Z, Deng S, Zhang L, Chen S, Lu Q, Peng H. Crocin protects against dexamethasone‑induced osteoblast apoptosis by inhibiting the ROS/Ca2+‑mediated mitochondrial pathway. Mol Med Rep 2019; 20:401-408. [PMID: 31115574 PMCID: PMC6580004 DOI: 10.3892/mmr.2019.10267] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Accepted: 02/28/2019] [Indexed: 12/18/2022] Open
Abstract
Osteoblast apoptosis has been identified as an important event in the development of glucocorticoid (GC)‑induced osteoporosis and osteonecrosis of the femoral head. Crocin, a bioactive ingredient of saffron, has been demonstrated to induce antiapoptotic effects on numerous types of cell in vitro; however, the effects of crocin on the dexamethasone (Dex)‑induced apoptosis of osteoblasts remain unclear. In the present study, the protective effects of crocin during Dex‑induced apoptosis of MC3T3‑E1 osteoblasts, and the underlying mechanisms, were investigated. MTT and Annexin V‑FITC/PI flow cytometry assays were performed to evaluate the viability and apoptosis of cells, respectively. The mitochondrial transmembrane potential, reactive oxygen species (ROS), intracellular Ca2+ levels and apoptosis‑associated protein expression were assessed via flow cytometry, fluorescence microscopy and western blotting. It was demonstrated that crocin pretreatment inhibited Dex‑induced apoptosis of osteoblasts in a dose‑dependent manner. Crocin reversed Dex‑induced decreases in the mitochondrial transmembrane potential, and increases in ROS and intracellular Ca2+ levels. Furthermore, crocin upregulated the expression levels of B‑cell lymphoma-2 (Bcl‑2) and mitochondrial cytochrome c (Cyt C), and downregulated those of cleaved caspase‑9, cleaved caspase‑3, Bcl‑2‑associated X protein and cytoplasmic Cyt C. N‑acetylcysteine, a ROS inhibitor, and 1,2‑bis(2‑aminophenoxy)ethane‑N,N,N',N'‑tetraacetic acid, a calcium chelator, attenuated Dex‑induced osteoblast apoptosis, whereas H2O2 and ionomycin, a calcium ionophore that increases intracellular calcium levels, reversed the antiapoptotic effects of crocin on Dex‑treated osteoblasts. These results indicated that crocin may protect osteoblasts from Dex‑induced apoptosis by inhibiting the ROS/Ca2+‑mediated mitochondrial pathway, thus suggesting that crocin has potential value as a treatment for GC‑induced bone diseases.
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Affiliation(s)
- Zhigang Nie
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Shuang Deng
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Lei Zhang
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Sen Chen
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Qiang Lu
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
| | - Hao Peng
- Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
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15
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Nateghi R, Alizadeh A, Jafari Ahangari Y, Fathi R, Akhlaghi A. Stimulatory effects of fish oil and vitamin E on ovarian function of laying hen. ITALIAN JOURNAL OF ANIMAL SCIENCE 2018. [DOI: 10.1080/1828051x.2018.1551071] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- Reihaneh Nateghi
- Faculty of Animal Science, Gorgan University of Agricultural Science and Natural Resource, Gorgan, Iran
| | - AliReza Alizadeh
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Yousef Jafari Ahangari
- Faculty of Animal Science, Gorgan University of Agricultural Science and Natural Resource, Gorgan, Iran
| | - Rouhollah Fathi
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Amir Akhlaghi
- Department of Animal Science College of Agriculture, Shiraz University, Shiraz, Iran
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16
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Li J, Wu DD, Zhang JX, Wang J, Ma JJ, Hu X, Dong WG. Mitochondrial pathway mediated by reactive oxygen species involvement in α-hederin-induced apoptosis in hepatocellular carcinoma cells. World J Gastroenterol 2018; 24:1901-1910. [PMID: 29740205 PMCID: PMC5937207 DOI: 10.3748/wjg.v24.i17.1901] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 04/04/2018] [Accepted: 04/09/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the antitumor activity of α-hederin in hepatocellular carcinoma (HCC) cells and its underlying mechanisms in vitro and in vivo.
METHODS SMMC-7721, HepG-2 and Huh-7 HCC cells were cultured in vitro and treated with α-hederin (0, 5 μmol/L, 10 μmol/L, 15 μmol/L, 20 μmol/L, 25 μmol/L, 30 μmol/L, 35 μmol/L, 40 μmol/L, 45 μmol/L, 50 μmol/L, 55 μmol/L, or 60 μmol/L) for 12 h, 24 h, or 36 h, and cell viability was then detected by the Cell Counting Kit-8. SMMC-7721 cells were treated with 0, 5 μmol/L, 10 μmol/L, or 20 μmol/L α-hederin for 24 h with or without DL-buthionine-S,R-sulfoximine (2 mmol/L) or N-acetylcysteine (5 mmol/L) pretreatment for 2 h, and additional assays were subsequently performed. Apoptosis was observed after Hoechst staining. Glutathione (GSH) and adenosine triphosphate (ATP) levels were measured using GSH and ATP Assay Kits. Intracellular reactive oxygen species (ROS) levels were determined by measuring the oxidative conversion of 2’,7’-dichlorofluorescin diacetate. Disruption of the mitochondrial membrane potential was evaluated using JC-1 staining. The protein levels of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, apoptosis-inducing factor and cytochrome C were detected by western blotting. The antitumor efficacy of α-hederin in vivo was evaluated in a xenograft tumor model.
RESULTS The α-hederin treatment induced apoptosis of HCC cells. The apoptosis rates in the control, low-dose α-hederin (5 μmol/L), mid-dose α-hederin (10 μmol/L) and high-dose α-hederin (20 μmol/L) groups were 0.90% ± 0.26%, 12% ± 2.0%, 21% ± 2.1% and 37% ± 3.8%, respectively (P < 0.05). The α-hederin treatment reduced intracellular GSH and ATP levels, induced ROS, disrupted the mitochondrial membrane potential, increased the protein levels of Bax, cleaved caspase-3, cleaved caspase-9, apoptosis-inducing factor and cytochrome C, and decreased Bcl-2 expression. The α-hederin treatment also inhibited xenograft tumor growth in vivo.
CONCLUSION The α-hederin saponin induces apoptosis of HCC cells via the mitochondrial pathway mediated by increased intracellular ROS and may be an effective treatment for human HCC.
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Affiliation(s)
- Jiao Li
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Central Laboratory of Renmin Hospital, Wuhan 430060, Hubei Province, China
| | - Dan-Dan Wu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Central Laboratory of Renmin Hospital, Wuhan 430060, Hubei Province, China
| | - Ji-Xiang Zhang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Central Laboratory of Renmin Hospital, Wuhan 430060, Hubei Province, China
| | - Jing Wang
- Department of Gastroenterology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China
| | - Jing-Jing Ma
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Central Laboratory of Renmin Hospital, Wuhan 430060, Hubei Province, China
| | - Xue Hu
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Central Laboratory of Renmin Hospital, Wuhan 430060, Hubei Province, China
| | - Wei-Guo Dong
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
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Wang X, Ding G, Lai W, Liu S, Shuai J. MicroRNA-383 upregulation protects against propofol-induced hippocampal neuron apoptosis and cognitive impairment. Exp Ther Med 2018; 15:3181-3188. [PMID: 29545833 PMCID: PMC5840935 DOI: 10.3892/etm.2018.5838] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 05/11/2017] [Indexed: 11/20/2022] Open
Abstract
Anesthesia-induced cognitive impairment is a recognized clinical phenomenon. The present study aimed to investigate the effect of microRNA-383 (miR-383) expression on propofol-induced learning and memory impairment. In total, 48 male Sprague-Dawley rats (weight, 250±10 g) were randomly divided into four groups (n=12 each): Control group, and three groups of rats that were anesthetized with propofol for 6 h and untreated (propofol model group), treated with a constructed lentivirus vector expressing miR-383 mimics (mimic + propofol group), or treated with miR-383 scramble (scramble + propofol group). The learning memory ability, hippocampal neuron apoptosis and expression of apoptosis-associated factors were detected using reverse transcription-quantitiative polymerase chain reaction and western blot analysis. Propofol treatment significantly reduced the relative mRNA and protein expression of miR-383, induced neuron apoptosis, upregulated the Bax/Bcl-2 ratio, downregulated the relative mRNA and protein expression levels of postsynaptic density protein 95 and cAMP-response element binding protein, and inactivated the phosphoinositide 3-kinase/protein kinase B signaling pathway. By contrast, miR-383 mimics significantly altered the propofol-induced dysregulation of the aforementioned factors. In conclusion, miR-383 mimic was able to repair propofol-induced cognitive impairment via protecting against hippocampal neuron apoptosis and dysregulation of related factors. The present study suggested that miR-383 may be used as a potential therapeutic target for the clinical treatment of cognitive impairment induced by propofol anesthesia.
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Affiliation(s)
- Xinlei Wang
- Department of Anesthesia, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
| | - Guoyou Ding
- Department of Anesthesia, Chinese People's Liberation Army No. 94 Hospital, Nanchang, Jiangxi 330002, P.R. China
| | - Wei Lai
- Department of Anesthesia, Chinese People's Liberation Army No. 94 Hospital, Nanchang, Jiangxi 330002, P.R. China
| | - Shiwen Liu
- Department of Anesthesia, Ganzhou People's Hospital, Ganzhou, Jiangxi 310000, P.R. China
| | - Jun Shuai
- Department of Anesthesia, Chinese People's Liberation Army No. 94 Hospital, Nanchang, Jiangxi 330002, P.R. China
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18
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Nagahora N, Yamada H, Kikuchi S, Hakozaki M, Yano A. Nrf2 Activation by 5-lipoxygenase Metabolites in Human Umbilical Vascular Endothelial Cells. Nutrients 2017; 9:nu9091001. [PMID: 28892009 PMCID: PMC5622761 DOI: 10.3390/nu9091001] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 09/01/2017] [Accepted: 09/07/2017] [Indexed: 12/14/2022] Open
Abstract
5-hydroxyeicosatetraenoic acid (5-HETE) and 5-hydroxyeicosapentaenoic acid (5-HEPE) are major metabolites produced by 5-lipoxygenase (5-LOX) from arachidonic acid (AA) and eicosapentaenoic acid (EPA). Effects of hydroxides on endothelial cells are unclear, although 5-LOX is known to increase at arteriosclerotic lesions. To investigate the effects of hydroxides on human umbilical vein endothelial cells (HUVECs), the cells were treated with 50 μM each of AA, EPA, 5-HETE, and 5-HEPE. Treatment of HUVECs with 5-HETE and 5-HEPE, rather than with AA and EPA, increased the nuclear translocation of NF-E2 related factor 2 (Nrf2) and upregulated the expression of heme oxygenase-1 and cystine/glutamate transporter regulated by Nrf2. Reactive oxygen species (ROS) generation was markedly elevated in HUVECs after treatment with 5-HETE and 5-HEPE, and the pretreatment with α-tocopherol abrogated ROS levels similar to those in the vehicle control. However, ROS generation was independent of Nrf2 activation induced by 5-HETE and 5-HEPE. 5-HETE was converted to 5-oxo-eicosatetraenoic acid (5-oxo-ETE) in HUVECs, and 5-oxo-ETE increased Nrf2 activation. These results suggest that 5-HETE works as an Nrf2 activator through the metabolite 5-oxo-ETE in HUVECs. Similarly, 5-HEPE works in the same way, because 5-HEPE is metabolized to 5-oxo-eicosapentaenoic acid through the same pathway as that for 5-HETE.
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Affiliation(s)
- Nozomi Nagahora
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
| | - Hidetoshi Yamada
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
| | - Sayaka Kikuchi
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
| | - Mayuka Hakozaki
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
| | - Akira Yano
- Iwate Biotechnology Research Center, 22-174-4 Narita, Kitakami, Iwate 024-0003, Japan.
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19
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de Oliveira MR, Nabavi SF, Nabavi SM, Jardim FR. Omega-3 polyunsaturated fatty acids and mitochondria, back to the future. Trends Food Sci Technol 2017. [DOI: 10.1016/j.tifs.2017.06.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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20
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Han L, Song S, Niu Y, Meng M, Wang C. Eicosapentaenoic Acid (EPA) Induced Macrophages Activation through GPR120-Mediated Raf-ERK1/2-IKKβ-NF-κB p65 Signaling Pathways. Nutrients 2017; 9:nu9090937. [PMID: 28841192 PMCID: PMC5622697 DOI: 10.3390/nu9090937] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 08/23/2017] [Accepted: 08/24/2017] [Indexed: 11/25/2022] Open
Abstract
Objectives: To investigate the immunomodulatory effect and molecular mechanisms of Eicosapentaenoic acid (EPA, a typical kind of n-3PUFAs) on RAW264.7 cells. Methods: A variety of research methods, including the RAW264.7 cells culture, cell proliferation assays, morphologic observations, measurements of NO production, cytokine assays, nuclear protein extractions, western blot analyses and NF-κB p65 immunofluorescence assays were used in this study. Results: The results showed that EPA could increase the proliferation index and enhance the release of nitric oxide (NO) and cytokines in RAW264.7 cells. Western blotting results revealed that the protein level of GPR120 increased significantly in RAW264.7 cells after EPA treatment. Meanwhile, EPA elevated the phosphorylation status of Raf, which may act as an upstream regulator of EPA-induced phosphorylated ERK1/2. In addition, the phosphorylated ERK1/2 may then promote IKKβ in endochylema and translocate the NF-κB p65 subunit into the nucleus, thus regulating the production of inducible nitric oxide synthase (iNOS) and cytokines. Conclusions: EPA (0.6–3.0 μmol) activates RAW264.7 cells through GPR120-mediated Raf-ERK1/2-IKKβ-NF-κB p65 signaling pathways.
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Affiliation(s)
- Lirong Han
- Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457, China.
| | - Shumin Song
- Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457, China.
| | - Yabing Niu
- Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457, China.
| | - Meng Meng
- Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457, China.
| | - Chunling Wang
- Key Laboratory of Food Nutrition and Safety, Ministry of Education, College of food Engineering and Biotechnology, Tianjin University of Science and Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin 300457, China.
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21
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Oono K, Takahashi K, Sukehara S, Kurosawa H, Matsumura T, Taniguchi S, Ohta S. Inhibition of PC3 human prostate cancer cell proliferation, invasion and migration by eicosapentaenoic acid and docosahexaenoic acid. Mol Clin Oncol 2017; 7:217-220. [PMID: 28781788 DOI: 10.3892/mco.2017.1287] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 04/06/2017] [Indexed: 01/24/2023] Open
Abstract
The n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in fish oil, exert a number of beneficial effects, and they are used in the treatment of hyperlipidemia. In recent years, EPA and DHA have been found to affect cancer cell proliferation. In the present study, PC3 cells, which are androgen-independent prostate cancer cells that resemble castration-resistant prostate cancer cells, were used to investigate a possible novel treatment for castration-resistant prostate cancer. The PC3 cells were cultured and incubated with various concentrations of EPA or DHA. Cancer proliferation was confirmed by trypan blue microscopy. Invasion and migration assays were used in the upper chamber in PC3 cells, and serum-free medium and various concentrations of EPA or DHA were placed in the lower chamber in serum-containing medium. EPA and DHA decreased PC3 cell proliferation, invasion and migration. The effect of EPA on PC3 cells was dose-dependent and significant differences were observed at concentrations of 100 and 200 µg/ml. The effect of DHA on PC3 cells was similar to that of EPA. In the migration assay, EPA exerted almost no effects at 25 µg/ml, but migration was reduced at 50 µg/ml. Similar to EPA, DHA exerted almost no effects at 25 µg/ml, but further reduction was observed at the 50 µg/ml concentration. In the invasion assay, EPA at 25 µg/ml was not significantly different from the control, but suppressed invasion at 50 µg/ml. DHA decreased invasion compared with the control at 25 µg/ml, whereas invasion was significantly reduced at a DHA concentration of 50 µg/ml. In conclusion, it was demonstrated that EPA and DHA were effective in decreasing the proliferation, invasion and migration of prostate PC3 cancer cells. However, the detailed underlying mechanisms have not yet been fully elucidated.
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Affiliation(s)
- Keiichi Oono
- Department of Clinical Pathology, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan
| | - Katsuya Takahashi
- Department of Clinical Pathology, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan
| | - Saeka Sukehara
- Department of Clinical Pathology, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan
| | - Hirohito Kurosawa
- Department of Clinical Pathology, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan
| | - Tomio Matsumura
- Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Department of Advanced Medicine for Health Promotion, Shinshu University, Matsumoto, Nagano 390-8621, Japan.,Department of Molecular Oncology, Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan
| | - Shun'Ichiro Taniguchi
- Department of Comprehensive Cancer Therapy, School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan
| | - Shoichiro Ohta
- Department of Clinical Pathology, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama 350-0295, Japan
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22
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Liao PC, Tandarich LC, Hollenbeck PJ. ROS regulation of axonal mitochondrial transport is mediated by Ca2+ and JNK in Drosophila. PLoS One 2017; 12:e0178105. [PMID: 28542430 PMCID: PMC5436889 DOI: 10.1371/journal.pone.0178105] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 05/06/2017] [Indexed: 12/31/2022] Open
Abstract
Mitochondria perform critical functions including aerobic ATP production and calcium (Ca2+) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two. Using the Drosophila third instar larval nervous system as the in vivo model, we found that ROS inhibited mitochondrial axonal transport more specifically, primarily due to reduced flux and velocity, but did not affect transport of other organelles. To understand the mechanisms underlying these effects, we examined Ca2+ levels and the JNK (c-Jun N-terminal Kinase) pathway, which have been shown to regulate mitochondrial transport and general fast axonal transport, respectively. We found that elevated ROS increased Ca2+ levels, and that experimental reduction of Ca2+ to physiological levels rescued ROS-induced defects in mitochondrial transport in primary neuron cell cultures. In addition, in vivo activation of the JNK pathway reduced mitochondrial flux and velocities, while JNK knockdown partially rescued ROS-induced defects in the anterograde direction. We conclude that ROS have the capacity to regulate mitochondrial traffic, and that Ca2+ and JNK signaling play roles in mediating these effects. In addition to transport defects, ROS produces imbalances in mitochondrial fission-fusion and metabolic state, indicating that mitochondrial transport, fission-fusion steady state, and metabolic state are closely interrelated in the response to ROS.
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Affiliation(s)
- Pin-Chao Liao
- Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Lauren C. Tandarich
- Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America
| | - Peter J. Hollenbeck
- Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America
- * E-mail:
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23
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Dumas JF, Brisson L, Chevalier S, Mahéo K, Fromont G, Moussata D, Besson P, Roger S. Metabolic reprogramming in cancer cells, consequences on pH and tumour progression: Integrated therapeutic perspectives with dietary lipids as adjuvant to anticancer treatment. Semin Cancer Biol 2017; 43:90-110. [DOI: 10.1016/j.semcancer.2017.03.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Revised: 03/10/2017] [Accepted: 03/13/2017] [Indexed: 02/07/2023]
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24
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Cheng D, Wang R, Wang C, Hou L. Mung bean (Phaseolus radiatus L.) polyphenol extract attenuates aluminum-induced cardiotoxicity through an ROS-triggered Ca 2+/JNK/NF-κB signaling pathway in rats. Food Funct 2017; 8:851-859. [PMID: 28128384 DOI: 10.1039/c6fo01817c] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Aluminum (Al) has been linked to the development of some cardiovascular diseases and mung bean is a functional food with the ability to detoxify. We aimed to evaluate the preventive effect and possible underlying mechanisms of the mung bean polyphenol extract (MPE) on Al-induced cardiotoxicity. Control, AlCl3 (171.8 mg Al per kg body weight), MPE + AlCl3 (Al-treatment plus 200 mg MPE per kg body weight), and a group of MPE per se were used. Al intake induced a significant increase of serum CK and LDH activity and the level of Na+, Ca2+, malondialdehyde and advanced oxidation protein products in the AlCl3-treated rats' heart tissue. Administration of MPE significantly improved the integrity and normal ion levels of heart tissue, and attenuated oxidative damage and the accumulation of Al in Al-treated rats. MPE significantly inhibited Al-induced increase of myocardial p-JNK, cytoplasmic NF-κB, cytochrome C, and caspase-9 protein expressions. Therefore, these results showed that MPE has a cardiac protective effect against Al-induced biotoxicity through ROS-JNK and NF-κB-mediated caspase pathways. Furthermore, the stability constant for the vitexin-Al complex was analyzed (log K = log K1 + log K2 = 4.91 + 4.85 = 9.76). We found that MPE-mediated protection against Al-cardiotoxicity is connected both with MPE antioxidant and chelation properties.
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Affiliation(s)
- Dai Cheng
- Key Laboratory of Food Safety and Sanitation, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
| | - Ruhua Wang
- Key Laboratory of Food Safety and Sanitation, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
| | - Chunling Wang
- Key Laboratory of Food Safety and Sanitation, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
| | - Lihua Hou
- Key Laboratory of Food Safety and Sanitation, Ministry of Education, College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, People's Republic of China.
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25
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Fu G, Dai J, Zhang D, Zhu L, Tang X, Zhang L, Zhou T, Duan P, Quan C, Zhang Z, Song S, Shi Y. Di(2-ethylhexyl) phthalate induces apoptosis through mitochondrial pathway in GC-2spd cells. ENVIRONMENTAL TOXICOLOGY 2017; 32:1055-1064. [PMID: 27416487 PMCID: PMC5673478 DOI: 10.1002/tox.22304] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Revised: 05/25/2016] [Accepted: 05/29/2016] [Indexed: 05/12/2023]
Abstract
Di(2-ethylhexyl) phthalate (DEHP), a plasticizer of synthetic polymers, is a well-known endocrine disrupting chemical (EDC) and reproductive toxicant. Addressing the unclear mechanism of DEHP-induced reproductive dysfunction, this study used GC-2spd cells to investigate the molecular mechanism involved in the DEHP-induced toxicity in the male reproductive system. The results indicated that the apoptotic cell death was significantly induced by DEHP exposure over 100 μM. Furthermore, DEHP treatment could induce oxidative stress in GC-2spd cells involving in the decrease of superoxide dismutase (SOD) activity (200 μM) and glutathione peroxidase (GSH-Px) activity (50 and 100 μM). In addition, DEHP induction also caused the elevated ratios of Bax/Bcl-2, release of cytochrome c and decomposition of procaspase-3 and procaspase-9 in GC-2spd cells. Taken together, our work provided the evidence that DEHP exposure might induce apoptosis of GC-2spd cells via mitochondria pathway mediated by oxidative stress. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1055-1064, 2017.
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Affiliation(s)
- Guoqing Fu
- Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, 947 Heping Avenue, Wuhan, 430081, People’s Republic of China
| | - Juan Dai
- Department of Non-communicable chronic disease prevention and control, Wuhan Centers for Disease Prevention and Control, 24 Jianghan N.Road, Wuhan, 430015, People’s Republic of China
| | - Dayi Zhang
- Lancaster Environment Centre, Lancaster University, Lancaster, LA1 4YQ, United Kingdom
| | - Lishan Zhu
- Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, 947 Heping Avenue, Wuhan, 430081, People’s Republic of China
| | - Xiao Tang
- Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, 947 Heping Avenue, Wuhan, 430081, People’s Republic of China
| | - Ling Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, 947 Heping Avenue, Wuhan, 430081, People’s Republic of China
| | - Ting Zhou
- Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, 947 Heping Avenue, Wuhan, 430081, People’s Republic of China
| | - Peng Duan
- Department of Occupational and Environmental Health, School of Public Health, Huazhong University of Science and Technology, Tongji Medical College, 13 Hangkong Road, Wuhan, Hubei 430030, People’s Republic of China
| | - Chao Quan
- Department of Occupational and Environmental Health, School of Public Health, Huazhong University of Science and Technology, Tongji Medical College, 13 Hangkong Road, Wuhan, Hubei 430030, People’s Republic of China
| | - Zhibing Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, 947 Heping Avenue, Wuhan, 430081, People’s Republic of China
- Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia 23298
| | - Shizhen Song
- Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, 947 Heping Avenue, Wuhan, 430081, People’s Republic of China
| | - Yuqin Shi
- Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, 947 Heping Avenue, Wuhan, 430081, People’s Republic of China
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Eicosapentaenoic acid induced SKOV-3 cell apoptosis through ERK1/2–mTOR–NF-κB pathways. Anticancer Drugs 2016; 27:635-42. [DOI: 10.1097/cad.0000000000000373] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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27
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The effect of the phenol compound ellagic acid on Ca2+ homeostasis and cytotoxicity in liver cells. Eur J Pharmacol 2016; 780:243-51. [DOI: 10.1016/j.ejphar.2016.03.057] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 03/24/2016] [Accepted: 03/29/2016] [Indexed: 01/21/2023]
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Tajeddine N. How do reactive oxygen species and calcium trigger mitochondrial membrane permeabilisation? Biochim Biophys Acta Gen Subj 2016; 1860:1079-88. [DOI: 10.1016/j.bbagen.2016.02.013] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 02/16/2016] [Accepted: 02/22/2016] [Indexed: 10/22/2022]
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Yang L, Sui W, Li Y, Qi X, Wang Y, Zhou Q, Gao H. Substance P Inhibits Hyperosmotic Stress-Induced Apoptosis in Corneal Epithelial Cells through the Mechanism of Akt Activation and Reactive Oxygen Species Scavenging via the Neurokinin-1 Receptor. PLoS One 2016; 11:e0149865. [PMID: 26901348 PMCID: PMC4762577 DOI: 10.1371/journal.pone.0149865] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 02/06/2016] [Indexed: 11/29/2022] Open
Abstract
Hyperosmolarity has been recognized as an important pathological factor in dry eye leading to ocular discomfort and damage. As one of the major neuropeptides of corneal innervation, substance P (SP) has been shown to possess anti-apoptotic effects in various cells. The aim of this study was to determine the capacity and mechanism of SP against hyperosmotic stress-induced apoptosis in cultured corneal epithelial cells. The cells were exposed to hyperosmotic stress by the addition of high glucose in the presence or absence of SP. The results showed that SP inhibited hyperosmotic stress-induced apoptosis of mouse corneal epithelial cells. Moreover, SP promoted the recovery of phosphorylated Akt level, mitochondrial membrane potential, Ca2+ contents, intracellular reactive oxygen species (ROS) and glutathione levels that impaired by hyperosmotic stress. However, the antiapoptotic capacity of SP was partially suppressed by Akt inhibitor or glutathione depleting agent, while the neurokinin-1 (NK-1) receptor antagonist impaired Akt activation and ROS scavenging that promoted by SP addition. In conclusion, SP protects corneal epithelial cells from hyperosmotic stress-induced apoptosis through the mechanism of Akt activation and ROS scavenging via the NK-1 receptor.
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Affiliation(s)
- Lingling Yang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China
| | - Wenjie Sui
- Shandong Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China
| | - Yunqiu Li
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China
| | - Xia Qi
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China
| | - Yao Wang
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China
| | - Qingjun Zhou
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China
- * E-mail: (HG); (QZ)
| | - Hua Gao
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China
- Shandong Eye Hospital, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China
- * E-mail: (HG); (QZ)
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30
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Chang HW, Tang JY, Yen CY, Chang HS, Huang HW, Chung YA, Chen IS, Huang MY. Synergistic anti-oral cancer effects of UVC and methanolic extracts of Cryptocarya concinna roots via apoptosis, oxidative stress and DNA damage. Int J Radiat Biol 2016; 92:263-72. [PMID: 26887975 DOI: 10.3109/09553002.2016.1145753] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Purpose Radiation combined with natural products may improve the radiosensitivity of cancer cells. This study investigated the potential of a combined modality treatment with Ultraviolet C (UVC; wavelength range 200-280 nm) and our previously identified anti-oral cancer agent (methanolic extracts of Cryptocarya concinna roots; MECCrt) in oral cancer cells. Materials and methods The mechanism of the possible synergy of UVC and MECCrt was explored in terms of cell viability, cell cycle, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MitoMP), and DNA damage analyses. Results In cell viability (%) at 24 h treatment, the low doses of UVC (14 J/m(2)) and MECCrt (10 μg/ml) resulted in slight damage to human oral cancer Ca9-22 cells (83.2 and 80.4) but was less harmful to human oral normal HGF-1 cells (93.4 and 91.8, respectively). The combined treatment of UVC and MECCrt (UVC/MECCrt) had a lower viability (54.5%) than UVC or MECCrt alone in Ca9-22 cells but no showed significant change in HGF-1 cells. In Ca9-22 cells, the expression of flow cytometry-based apoptosis (sub-G1 phase, annexin V, and pancaspase assays) was significantly higher in UVC/MECCrt than in UVC or MECCrt alone (p < 0.0001). Using flow cytometry, intracellular ROS levels of UVC/MECCrt and MECCrt alone were higher than for UVC alone. MitoMP change and H2A histone family member X (γH2AX; H2AFX)-based DNA damage were synergistically inhibited and induced by MECCrt/UVC compared to its single treatment in Ca9-22 cells, respectively. Conclusion UVC plus MECCrt treatment had selective killing and synergistic anti-proliferative effects against oral cancer cells involving apoptosis, oxidative stress, and DNA damage. This combination therapy appears to have a great clinical potential against oral cancer cells.
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Affiliation(s)
- Hsueh-Wei Chang
- a Department of Biomedical Science and Environmental Biology , Kaohsiung Medical University , Kaohsiung , Taiwan ;,b Institute of Medical Science and Technology, National Sun Yat-sen University , Kaohsiung , Taiwan ;,c Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung , Taiwan ;,d Center for Research Resources and Development, Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Jen-Yang Tang
- e Department of Radiation Oncology, Faculty of Medicine, College of Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan ;,f Department of Radiation Oncology , Kaohsiung Medical University , Kaohsiung , Taiwan ;,g Department of Radiation Oncology , Kaohsiung Municipal Ta-Tung Hospital , Kaohsiung , Taiwan
| | - Ching-Yu Yen
- h Department of Oral and Maxillofacial Surgery , Chi-Mei Medical Center , Tainan ;,i School of Dentistry , Taipei Medical University , Taipei
| | - Hsun-Shuo Chang
- j Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung , Taiwan ;,k School of Pharmacy, College of Pharmacy , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Hurng-Wern Huang
- l Institute of Biomedical Science, National Sun Yat-Sen University , Kaohsiung , Taiwan
| | - Yi-An Chung
- a Department of Biomedical Science and Environmental Biology , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Ih-Sheng Chen
- j Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University , Kaohsiung , Taiwan ;,k School of Pharmacy, College of Pharmacy , Kaohsiung Medical University , Kaohsiung , Taiwan
| | - Ming-Yii Huang
- e Department of Radiation Oncology, Faculty of Medicine, College of Medicine , Kaohsiung Medical University Hospital , Kaohsiung , Taiwan ;,f Department of Radiation Oncology , Kaohsiung Medical University , Kaohsiung , Taiwan
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31
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Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy. J Clin Med 2016; 5:jcm5020015. [PMID: 26821053 PMCID: PMC4773771 DOI: 10.3390/jcm5020015] [Citation(s) in RCA: 196] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Revised: 01/15/2016] [Accepted: 01/19/2016] [Indexed: 12/24/2022] Open
Abstract
Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, possibly improving their efficacy especially against cancers resistant to treatment. Moreover, in contrast to traditional therapies, n-3 PUFAs appear to cause selective cytotoxicity towards cancer cells with little or no toxicity on normal cells. This review focuses on studies investigating the cytotoxic activity of n-3 PUFAs against cancer cells via apoptosis, analyzing the molecular mechanisms underlying this effective and selective activity. Here, we highlight the multiple molecules potentially targeted by n-3 PUFAs to trigger cancer cell apoptosis. This analysis can allow a better comprehension of the potential cytotoxic therapeutic role of n-3 PUFAs against cancer, providing specific information and support to design future pre-clinical and clinical studies for a better use of n-3 PUFAs in cancer therapy, mainly combinational therapy.
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Yumnam S, Hong GE, Raha S, Saralamma VVG, Lee HJ, Lee WS, Kim EH, Kim GS. Mitochondrial Dysfunction and Ca(2+) Overload Contributes to Hesperidin Induced Paraptosis in Hepatoblastoma Cells, HepG2. J Cell Physiol 2015; 231:1261-8. [PMID: 26492105 DOI: 10.1002/jcp.25222] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Accepted: 10/20/2015] [Indexed: 11/11/2022]
Abstract
Paraptosis is a programmed cell death which is morphologically and biochemically different from apoptosis. In this study, we have investigated the role of Ca(2+) in hesperidin-induced paraptotic cell death in HepG2 cells. Increase in mitochondrial Ca(2+) level was observed in hesperidin treated HepG2 cells but not in normal liver cancer cells. Inhibition of inositol-1,4,5-triphosphate receptor (IP3 R) and ryanodine receptor also block the mitochondrial Ca(2+) accumulation suggesting that the release of Ca(2+) from the endoplasmic reticulum (ER) may probably lead to the increase in mitochondrial Ca(2+) level. Pretreatment with ruthenium red (RuRed), a Ca(2+) uniporter inhibitor inhibited the hesperidin-induced mitochondrial Ca(2+) overload, swelling of mitochondria, and cell death in HepG2 cells. It has also been demonstrated that mitochondrial Ca(2+) influxes act upstream of ROS and mitochondrial superoxide production. The increased ROS production further leads to mitochondrial membrane loss in hesperidin treated HepG2 cells. Taken together our results show that IP3 R and ryanodine receptor mediated release of Ca(2+) from the ER and its subsequent influx through the uniporter into mitochondria contributes to hesperidin-induced paraptosis in HepG2 cells.
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Affiliation(s)
- Silvia Yumnam
- Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, Republic of Korea
| | - Gyeong Eun Hong
- Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, Republic of Korea
| | - Suchismita Raha
- Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, Republic of Korea
| | - Venu Venkatarame Gowda Saralamma
- Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, Republic of Korea
| | - Ho Jeong Lee
- Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, Republic of Korea
| | - Won-Sup Lee
- Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea
| | - Eun-Hee Kim
- Department of Nursing Science, International University of Korea, Jinju, Republic of Korea
| | - Gon Sup Kim
- Research Institute of Life Science, College of Veterinary Medicine (BK21 plus project), Gyeongsang National University, Gazwa, Jinju, Republic of Korea
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33
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Antitumour activity of EPA-enriched phospholipids liposomes against S180 ascitic tumour-bearing mice. J Funct Foods 2015. [DOI: 10.1016/j.jff.2015.06.061] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
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Li WJ, Nie SP, Yao YF, Liu XZ, Shao DY, Gong DM, Cui SW, Phillips GO, He M, Xie MY. Ganoderma atrum Polysaccharide Ameliorates Hyperglycemia-Induced Endothelial Cell Death via a Mitochondria-ROS Pathway. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2015; 63:8182-8191. [PMID: 26323486 DOI: 10.1021/acs.jafc.5b03462] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
The aim of the present study was to examine the role of Ganoderma atrum polysaccharide (PSG-1) in reactive oxygen species (ROS) generation and mitochondrial function in hyperglycemia-induced angiopathy. In this work, ROS scavenger, oxidizing agent tert-butylhydroperoxide (tBH), mitochondrial permeability transition pore (mPTP) blockers, and caspase inhibition are used to investigate whether PSG-1 may promote survival of human umbilical vein cells (HUVECs) through preventing the overproduction of ROS and mitochondrial dysfunction. Experimental results show that exposure of HUVECs to 35.5 mmol/L glucose increases the proportion of cells undergoing apoptosis. PSG-1, mPTP blocker, or caspase inhibition can reduce apoptosis and ROS generation. PSG-1 also increases mitochondrial Bcl-2 protein formation and mitochondrial membrane potential (ΔΨm) but inhibits Bax translocation, cytochrome c release, and caspase activation. In summary, vascular protection of PSG-1 can be mediated by a mitochondria-ROS pathway. ROS generation and mPTP induction are critical for high glucose-mediated apoptosis. PSG-1 ameliorates endothelial dysfunction by inhibiting oxidative stress and subsequent mitochondrial dysfunction.
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Affiliation(s)
- Wen-Juan Li
- State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China
| | - Shao-Ping Nie
- State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China
| | - Yu-Fei Yao
- China People's Liberation Army No. 94 Hospital, No. 1028, Jinggangshan Avenue, Nanchang 330000, China
| | - Xiao-Zhen Liu
- State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China
| | - Deng-Yin Shao
- State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China
| | - De-Ming Gong
- State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China
- School of Biological Sciences, The University of Auckland , Auckland, Private Bag 92019, New Zealand
| | - Steve W Cui
- State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China
- Guelph Food Research Center, Agriculture and Agri-Food Canada, 93 Stone Road West, Guelph, Ontario, Canada N1G 5C9
| | - Glyn O Phillips
- Phillips Hydrocolloids Research Centre, Glyndwr University , Wrexham, LL11 2AW Wales, U.K
| | - Ming He
- State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China
- Departments of Pharmaceutical Science, Nanchang University , Nanchang 330006, China
| | - Ming-Yong Xie
- State Key Laboratory of Food Science and Technology, Nanchang University , 235 Nanjing East Road, Nanchang 330047, China
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35
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Ferguson LR. Nutritional Modulation of Gene Expression: Might This be of Benefit to Individuals with Crohn's Disease? Front Immunol 2015; 6:467. [PMID: 26441972 PMCID: PMC4566049 DOI: 10.3389/fimmu.2015.00467] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Accepted: 08/27/2015] [Indexed: 12/18/2022] Open
Abstract
The incidence of inflammatory bowel diseases (IBD), including Crohn's disease (CD), is increasing worldwide, especially in young children and adolescents. Although hospitalized patients are usually provided with enteral or parenteral support, continuing care typically requires a trial-and-error approach to suppressing symptoms and maintaining disease remission. Current nutritional advice does not differ from general population guidelines. International collaborative studies have revealed 163 distinct genetic loci affecting susceptibility to IBD, in some of which host-microbe interactions can be seen to play an important role. The nature of these loci enables a rationale for predicting nutritional requirements that may not be evident through standard therapeutic approaches. Certain recognized nutrients, such as vitamin D and long-chain omega-3 polyunsaturated fatty acids, may be required at higher than anticipated levels. Various phytochemicals, not usually considered in the same class as classic nutrients, could play an important role. Prebiotics and probiotics may also be beneficial. Genomic approaches enable proof of principle of nutrient optimization rather than waiting for disease symptoms to appear and/or progress. We suggest a paradigm shift in diagnostic tools and nutritional therapy for CD, involving a systems biology approach for implementation.
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Affiliation(s)
- Lynnette R Ferguson
- Discipline of Nutrition and Dietetics, Faculty of Medical and Health Sciences, The University of Auckland , Auckland , New Zealand ; Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland , Auckland , New Zealand
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