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Shaban NZ, El-Rashidy FH, Adam AH, Beltagy DM, Ali AE, Abde-Alaziz AA, Talaat IM. Anticancer role of mango (Mangifera indica L.) peel and seed kernel extracts against 7,12- dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rats. Sci Rep 2023; 13:7703. [PMID: 37169856 PMCID: PMC10175271 DOI: 10.1038/s41598-023-34626-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Accepted: 05/04/2023] [Indexed: 05/13/2023] Open
Abstract
Breast cancer is the second leading cause of cancer death among women. The present study is an effort to reveal the antiproliferative and antioxidant actions of mango seed kernel extract (KE), peel extract (PE), and their combination (KEPE) on mammary tumors induced by 7,12 dimethylbenz[a]anthracene (DMBA). Seven groups of adult female Sprague-Dawley rats were prepared, including C: (control), DMBA: (rats were administered with DMBA), (DMBA-KE), (DMBA-PE), and (DMBA-KEPE): rats were administered with DMBA and then treated with KE, PE, and (both KE and PE), respectively, (KE) and (PE): rats were administered with KE and PE, separately. The study focused on the assessment of markers of endocrine derangement [serum 17-β estradiol (E2)], apoptosis [caspase-3 and deoxyribonucleic acid fragmentation (DNAF)], and oxidative stress [lipid peroxidation and antioxidants (glutathione, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase)]. Histopathological examination and immunohistochemical expression of caspase-3 and estrogen receptor-α (ER-α) in mammary gland tissues (MGTs) were determined, as well as the characterization of mango extracts. The results showed that DMBA administration induced mammary tumors by increasing cell proliferation and evading apoptosis. In addition, DMBA administration caused oxidative stress by the production of reactive oxygen species, which increased lipid peroxidation and decreased cellular antioxidants, allowing cancer to progress. In contrast, treatment with DMBA-KE, DMBA-PE, or DMBA-KEPE diminished mammary tumors induced by DMBA, where they reduced oxidative stress via increased antioxidant parameters including reduced glutathione, superoxide dismutase, total glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Also, different treatments decreased proliferation through the reduction of E2, and ER-α expression levels. However, these treatments increased the apoptosis of unwanted cells as they increased caspase-3 activity and DNAF. All these changes led to the prevention of breast injuries and the reduction of mammary tumors. This demonstrates that the contents of mango extracts, especially phenolics and flavonoids, have an important role in mammary tumor treatment through their potential antioxidant, antiproliferative, proapoptotic, and anti-estrogenic effects. KE and PE administration for 4 weeks had no adverse effects. Conclusion: Each of KE, PE, and KEPE has a therapeutic effect against DMBA-induced mammary tumors via induction of apoptosis and reduction of each of the OS, proliferation, and estrogenic effects. So, they can play an important role in the pharmacological tole.
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Affiliation(s)
- Nadia Z Shaban
- Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt.
| | - Fatma H El-Rashidy
- Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, 21511, Egypt
| | - Amany H Adam
- Chemistry Department, Faculty of Science, Damanhour University, Damanhour, Egypt
| | - Doha M Beltagy
- Chemistry Department, Faculty of Science, Damanhour University, Damanhour, Egypt
| | - Alaa E Ali
- Chemistry Department, Faculty of Science, Damanhour University, Damanhour, Egypt
| | - Ahmed A Abde-Alaziz
- Endocrinology Unit, Department of Internal Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Iman M Talaat
- Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, UAE
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Prysyazhnyuk V, Sydorchuk L, Sydorchuk R, Prysiazhniuk I, Bobkovych K, Buzdugan I, Dzuryak V, Prysyazhnyuk P. Glutathione-S-transferases genes-promising predictors of hepatic dysfunction. World J Hepatol 2021; 13:620-633. [PMID: 34239698 PMCID: PMC8239493 DOI: 10.4254/wjh.v13.i6.620] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/06/2021] [Accepted: 06/03/2021] [Indexed: 02/06/2023] Open
Abstract
One of the most commonly known genes involved in chronic diffuse liver diseases pathogenesis are genes that encodes the synthesis of glutathione-S-transferase (GST), known as the second phase enzyme detoxification system that protects against endogenous oxidative stress and exogenous toxins, through catalisation of glutathione sulfuric groups conjugation and decontamination of lipid and deoxyribonucleic acid oxidation products. The group of GST enzymes consists of cytosolic, mitochondrial and microsomal fractions. Recently, eight classes of soluble cytoplasmic isoforms of GST enzymes are widely known: α-, ζ-, θ-, κ-, μ-, π-, σ-, and ω-. The GSTs gene family in the Human Gene Nomenclature Committee, online database recorded over 20 functional genes. The level of GSTs expression is considered to be a crucial factor in determining the sensitivity of cells to a broad spectrum of toxins. Nevertheless, human GSTs genes have multiple and frequent polymorphisms that include the complete absence of the GSTM1 or the GSTT1 gene. Current review supports the position that genetic polymorphism of GST genes is involved in the pathogenesis of various liver diseases, particularly non-alcoholic fatty liver disease, hepatitis and liver cirrhosis of different etiology and hepatocellular carcinoma. Certain GST allelic variants were proven to be associated with susceptibility to hepatological pathology, and correlations with the natural course of the diseases were subsequently postulated.
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Affiliation(s)
- Vasyl Prysyazhnyuk
- Department of Propedeutics of Internal Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine.
| | - Larysa Sydorchuk
- Department of Family Medicine, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Ruslan Sydorchuk
- Department of Surgery, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Iryna Prysiazhniuk
- Department of Internal Medicine and Invectious Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Kateryna Bobkovych
- Department of Propedeutics of Internal Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Inna Buzdugan
- Department of Internal Medicine and Invectious Diseases, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Valentina Dzuryak
- Department of Family Medicine, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
| | - Petro Prysyazhnyuk
- Department of Medical and Pharmaceutical Chemistry, Bukovinian State Medical University, Chernivtsi 58002, Chernivtsi region, Ukraine
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Udayantha HMV, Liyanage DS, Nadarajapillai K, Omeka WKM, Yang H, Jeong T, Lee J. Molecular characterization, immune and xenobiotic responses of glutathione S-transferase omega 1 from the big-belly seahorse: Novel insights into antiviral defense. FISH & SHELLFISH IMMUNOLOGY 2021; 109:62-70. [PMID: 33348035 DOI: 10.1016/j.fsi.2020.12.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 12/10/2020] [Accepted: 12/16/2020] [Indexed: 06/12/2023]
Abstract
Glutathione S-transferases (GSTs) are important enzymes involved in phase II detoxification and function by conjugating with the thiol group of glutathione. In this study, we isolated an omega class GST from the big-belly seahorse (Hippocampus abdominalis; HaGSTO1) to study the putative xenobiotic responses and defense ability against viral and bacterial infections in this animal. The isolated HaGSTO1 gene, with a cording sequence of 720 bp, encodes a peptide of 239 amino acids. The predicted molecular mass and theoretical isoelectric point of HaGSTO1 was 27.47 kDa and 8.13, respectively. In-silico analysis of HaGSTO1 revealed a characteristic N-terminal thioredoxin-like domain and a C-terminal domain. Unlike other GSTs, the C-terminal of HaGSTO1 reached up to the N-terminal, and the N-terminal functional group was cysteine rather than tyrosine or serine, as observed in other GSTs. Phylogenetic analysis showed the evolutionary proximity of HaGSTO1 with other identified vertebrate and invertebrate GST orthologs. For the first time, we demonstrated the viral defense capability of HaGSTO1 against viral hemorrhagic septicemia virus (VHSV) infection. All six nucleoproteins of VHSV were significantly downregulated in HaGSTO1-overexpressing FHM cells at 24 h after infection compared with those in the control. Moreover, arsenic toxicity was significantly reduced in HaGSTO1-overexpressing FHM cells, and cell viability increased. Real-time polymerase chain reaction analysis showed that HaGSTO1 transcripts were highly expressed in the pouch and gill when compared with those in other tissues. Blood HaGSTO1 transcripts were significantly upregulated after Edwardsiella tarda, Streptococcus iniae, lipopolysaccharide, and polyinosinic:polycytidylic acid challenge experiments. Collectively, these findings suggest the involvement of HaGSTO1 in the host defense mechanism of seahorses.
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Affiliation(s)
- H M V Udayantha
- Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province, 63243, Republic of Korea
| | - D S Liyanage
- Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province, 63243, Republic of Korea
| | - Kishanthini Nadarajapillai
- Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province, 63243, Republic of Korea
| | - W K M Omeka
- Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province, 63243, Republic of Korea
| | - Hyerim Yang
- Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province, 63243, Republic of Korea
| | - Taehyug Jeong
- Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province, 63243, Republic of Korea; Marine Science Institute, Jeju National University, Jeju Self-Governing Province, 63333, Republic of Korea
| | - Jehee Lee
- Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju Self-Governing Province, 63243, Republic of Korea; Marine Science Institute, Jeju National University, Jeju Self-Governing Province, 63333, Republic of Korea.
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Wang LK, Yue HL, Peng XJ, Zhang SJ. GSTO1 regards as a meritorious regulator in cutaneous malignant melanoma cells. Mol Cell Probes 2019; 48:101449. [PMID: 31525447 DOI: 10.1016/j.mcp.2019.101449] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 09/12/2019] [Accepted: 09/12/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Glutathione S-transferase omega 1 (GSTO1), as a member of the glutathione S-transferase (GST) family genes, has been discovered to be up-regulated in several cancer cell lines which exhibited strong aggressiveness. However, the function of GSTO1 on cutaneous malignant melanoma (CMM) has not been illuminated. METHODS Outcome of expression level and prognosis of GSTO1 were obtained from Oncomine and TCGA database. The specific effects of GSTO1 on the characteristics and regulatory mechanism of CMM cells were demonstrated by cell counting kit-8, colony formation, flow cytometry, and transwell assays in vitro. Western blot was employed to analyze the expression of proliferating cell nuclear antigen (PCNA), p53 and epithelial-to-mesenchymal (EMT) related proteins. RESULTS We observed that GSTO1 was up-regulated in CMM samples when compared with the corresponding controls. Moreover, patients in CMM with high expression of GSTO1 were more likely to have a poor prognosis. Through in vitro experiments, silenced GSTO1 resulted in inhibition of CMM cells growth and aggressiveness, increased cell apoptosis, and blocked cell cycle. Finally, the expression of PCNA, p53 and EMT-related proteins were changed due to reduction of GSTO1. CONCLUSIONS To sum up, our outcomes exhibited that weakening GSTO1 reduced the proliferation and mobility of CMM cells, increased the apoptosis ability of CMM cells, and arrested cell cycle at G1 phase, which can be achieved by affecting the expression of PCNA, p53 and the EMT process. This discovery provided a new perspective for elucidating the mechanism of CMM, and offered theoretical support for searching clinical therapeutic targets in the future.
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Affiliation(s)
- Li-Kun Wang
- Department of Dermatology, North China University of Science and Technology Affiliated Hospital, China.
| | - Hai-Long Yue
- Department of Anesthesiology, Kailuan General Hospital, China
| | - Xiao-Jing Peng
- Department of Anesthesiology, Kailuan General Hospital, China
| | - Shu-Juan Zhang
- Department of Anesthesiology, Kailuan General Hospital, China
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Gao YH, Li QQ, Wang CG, Sun J, Wang XM, Li YJ, He XT, Xu HQ, Niu JQ. The role of IL22 polymorphisms on liver cirrhosis in patients with hepatitis B virus: A case control study. Medicine (Baltimore) 2019; 98:e17867. [PMID: 31689880 PMCID: PMC6946515 DOI: 10.1097/md.0000000000017867] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 09/14/2019] [Accepted: 10/08/2019] [Indexed: 01/12/2023] Open
Abstract
AIMS Interleukin(IL)-22 plays an important role in promoting liver regeneration and repair, but its role in chronic HBV-related liver diseasesis not clear. The goal of this study was to evaluate associations between eight IL22 single nucleotide polymorphisms (SNPs) and the development of chronic HBV cirrhosis and HBV-related HCC within a Chinese Han population. METHODS We investigated associations between single nucleotide polymorphisms (SNPs) in the IL22 gene (rs1026788, rs2227472, rs2227491, rs2227485, rs1179249, rs2046068,rs2227473, and rs7314777) and the risk of HBV-related chronic liver diseases within a Han population in Northeast China. A total of 649 participants were included in the study, including 103 patients with CHB, 264 patients with LC, and 282 patients with HCC. The odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated using chi-square test. Haplotype analysis was conducted by haploview software. RESULTS Genotype and allele distributions of SNPs rs1179249 and rs2227472 differed between LC and CHB groups (both P < 0.05).The G alleles of SNP rs2227491 and rs1026788 were more frequent in the LC group than in the CHB group (P = 0.046, P = 0.041 respectively). A IL22 haplotype consisting of the minor alleles of SNP rs1179249 and the major alleles of seven other SNPs occurred less frequently in the LC and HCC groups than in the CHB group (28.2%, 33.94%, and 37.86%, respectively, P < 0.05). Moreover, there were no significant associations between smoking or drinking and IL22 SNPs on the risk of HCC (P > 0.05). CONCLUSION IL22 genetic variations were associated with chronic HBV infection progression, especially in the HBV-LC group. The IL22 genetic variations may help clinicians initiate the correct treatment strategy at the CHB stage.
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Affiliation(s)
- Yan-Hang Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun
| | - Qing-Quan Li
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun
- Department of Gastroenterology, The Hospital of CNOOC, Tianjin
| | - Chun-Guang Wang
- Department of Surgery, The Second Hospital of Jilin University, Changchun, Jilin
| | - Jing Sun
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun
- Department of Gastroenterology, Heping Hospital, Changzhi Medical College, Changzhi, Shanxi
| | - Xiao-Mei Wang
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun
| | - Ya-Jun Li
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun
| | - Xiu-Ting He
- Department of Geriatrics, The First Hospital of Jilin University
| | - Hong-Qin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun
| | - Jun-Qi Niu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun
- Jilin Province Key Laboratory of Infectious Diseases, Laboratory of Molecular Virology, Changchun, Jilin Province, China
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Bender D, Hildt E. Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis. Int J Mol Sci 2019; 20:ijms20184659. [PMID: 31546975 PMCID: PMC6769940 DOI: 10.3390/ijms20184659] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 09/16/2019] [Accepted: 09/17/2019] [Indexed: 12/15/2022] Open
Abstract
With respect to their genome and their structure, the human hepatitis B virus (HBV) and hepatitis C virus (HCV) are complete different viruses. However, both viruses can cause an acute and chronic infection of the liver that is associated with liver inflammation (hepatitis). For both viruses chronic infection can lead to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Reactive oxygen species (ROS) play a central role in a variety of chronic inflammatory diseases. In light of this, this review summarizes the impact of both viruses on ROS-generating and ROS-inactivating mechanisms. The focus is on the effect of both viruses on the transcription factor Nrf2 (nuclear factor erythroid 2 (NF-E2)-related factor 2). By binding to its target sequence, the antioxidant response element (ARE), Nrf2 triggers the expression of a variety of cytoprotective genes including ROS-detoxifying enzymes. The review summarizes the literature about the pathways for the modulation of Nrf2 that are deregulated by HBV and HCV and describes the impact of Nrf2 deregulation on the viral life cycle of the respective viruses and the virus-associated pathogenesis.
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Affiliation(s)
- Daniela Bender
- Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Straβe 51-59, D-63225 Langen, Germany.
| | - Eberhard Hildt
- Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Straβe 51-59, D-63225 Langen, Germany.
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Abdolmohammadi R, Shahbazi Azar S, Khosravi A, Shahbazi M. CCR5 Polymorphism as a Protective Factor for Hepatocellular Carcinoma in Hepatitis B Virus-Infected Iranian Patients. Asian Pac J Cancer Prev 2016; 17:4643-4646. [PMID: 27892677 PMCID: PMC5454610 DOI: 10.22034/apjcp.2016.17.10.4643] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
The CC chemokine receptor 5 (CCR5) delta 32 allele results in a nonfunctional form of the chemokine receptor and has been implicated in a variety of immune-mediated diseases. CCR5Δ32 may also predispose one to chronic liver disease or be linked with resistance to HBV infection. This study was undertaken to investigate any association between CCR5 polymorphism with resistance to hepatitis B or susceptibility to HBV infection. A total of 812 Iranian individuals were enrolled into two groups: HBV infected cases (n=357), who were HBsAg-positive, and healthy controls (n=455). We assessed polymorphisms in the CCR5 gene using specific CCR5 oligonucleotide primers surrounding the breakpoint deletion. Genotype distributions of the HBV infected cases and healthy controls were determined and compared. The CCR5/CCR5 (WW) and CCR5/CCR5Δ32 (W/D) genotypes were found in (98%) and (2%) of HBV infected cases, respectively. The CCR5 Δ32/Δ32genotype was not found in HBV infected cases. Genotype distributions of CCR5 in healthy controls were W/W genotype in (87.3%), W/D genotype in (11.2%) and D/D genotype in (1.5%). Heterozygosity for CCR5/CCR5Δ32 (W/D) in healthy controls was greater than in HBV infected cases (11.2% vs 2%, p < 0.001). W/D and D/D genotypes were more prominent in healthy controls than in HBV infected cases. This study provides evidence that the CCR5Δ32 polymorphism may have a protective effect in resistance to HBV infection at least in the Iranian population.
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Affiliation(s)
- Reza Abdolmohammadi
- Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
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