Search

Baran Marzena, Miziak Paulina, Bonio Katarzyna. Histone deacetylase inhibitors. Journal of Education, Health and Sport. 2020;10(8):361‑364. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.08.043 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.08.043 https://zenodo.org/record/3996503 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 01.08.2020. Revised: 05.08.2020. Accepted: 23.08.2020. Histone deacetylase inhibitors Marzena Baran1, Paulina Miziak1, Katarzyna Bonio2 1Chair and Department of Biochemistry and Molecular Biology, Medical University of Lublin 2Department of Cell Biology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin Abstract The human genome is contained in chromatin, which is a complex macromolecular complex. It is made of DNA, histones and non-histone proteins. The structure of chromatin and the process of its rearrangement regulate the process of transcription, and hence gene expression. Deacetylase (HDAC) is a group of enzymes that catalyzes the cleavage of acetyl groups from lysine residues in histone and nonhistone proteins. This reaction is catalyzed by zinc or NAD + ions [3]. Histone deacetylases are present in the cytoplasm or nucleus of eukaryotes [4, 5]. These enzymes have been divided into 5 classes (I, IIa, IIb, III and IV) due to the similarity in structure and origin. Vorinostat is one of the most studied HDAC inhibitors. It belongs to the second generation polar-planar hydroxamic acid derivatives that inhibit class I and II histone deacetylases. Panobinostat and belinostat are HDAC inhibitors derived from hydroxamic acid that have also entered clinical trials. Valproic acid, from the group of aliphatic acids, belongs to inhibitors of class I and IIα deacetylases and is an established drug anticonvulsants. Histone deacetylase inhibitors may be useful in the treatment of neoplasms because they influence the action of factors related to cell proliferation, may cause cell cycle arrest, and coordinate the action of apoptotic factors and induce apoptosis. There are several deacetylase inhibitors available as drugs and are in different phases of clinical trials. They differ in potency and enzyme specificity. However, it is still unknown which deacetylases are essential for initiating and sustaining metabolic pathways leading to tumor development. Key words: inhibitors, histone deacetylase, cancer

Baran Marzena, Miziak Paulina, Bonio Katarzyna. Sirtuin as the target of anti-cancer therapy. Journal of Education, Health and Sport. 2020;10(8):240-243. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.08.027 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.08.027 https://zenodo.org/record/3987512 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 01.08.2020. Revised: 05.08.2020. Accepted: 17.08.2020. Sirtuin as the target of anti-cancer therapy Marzena Baran1, Paulina Miziak1, Katarzyna Bonio2 1Chair and Department of Biochemistry and Molecular Biology, Medical University of Lublin 2 Department of Cell Biology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin Abstract Sirtuins is a group of nicotinamide dinucleotide (NAD +) - dependent, which have deacetylation and ADP-ribosylation activity. They work by detaching the acetyl group from the lysine residue of the histones, thanks to which they influence the control of gene expression. There are 7 classes of sirtuins due to the type of enzymatic activity and the cellular compartment in which they occur. They have a significant impact on the cell cycle, cellular process, including glucose metabolism, fat differentiation, fatty acid oxidation, neurogenesis, carcinogenesis and the aging process. Due to its unique properties, compounds are sought that can control the concentration of sirtuins in the body. One of such substances is resveratrol. It is a naturally occurring polyphenol that has a number of positive effects on the body. It works by increasing the concentration of NAD +, which is a sirtuin cofactor. It occurs naturally, and its greatest concentration is found in grapes and peanuts. It has a beneficial effect in the treatment of pancreatic, colon, breast, prostate and liver cancer. Research indicates that there is a potential for resveratrol supplementation to have positive health effects. However, there is still a need for more research on resveratrol, particularly in animal models. Determining the effectiveness of this chemical as an anti-cancer agent can be a major area of research and clinical trials. Key words: sirtuin, deacetylation, histone deacetylase, resveratrol

Triple-negative breast cancers (TNBCs) are histologically heterogenic invasive carcinomas of no specific type that lack distinctive histological characteristics. The prognosis for women with TNBC is poor. Regardless of the applied treatments, recurrences and deaths are observed 3–5 years after the diagnosis. Thus, new diagnostic markers and targets for personalized treatment are needed. The subject of our study—the Kaiso transcription factor has been found to correlate with the invasion and progression of breast cancer. The publicly available TCGA breast cancer cohort containing Illumina HiSeq RNAseq and clinical data was explored in the study. Additionally, Kaiso protein expression was assessed in formalin-fixed and paraffin-embedded tissue archive specimens using the tissue microarray technique. In this retrospective study, Kaiso protein expression (nuclear localization) was compared with several clinical factors in the cohort of 103 patients with TNBC with long follow-up time. In univariate and multivariate analysis, high Kaiso protein but not mRNA expression was correlated with better overall survival and disease-free survival, as well as with premenopausal age. The use of radiotherapy was correlated with better disease-free survival (DFS) and overall survival (OS). However, given the heterogeneity of TNBC and context-dependent molecular diversity of Kaiso signaling in cancer progression, these results must be taken with caution and require further studies.

Baran Marzena, Miziak Paulina, Bonio Katarzyna. Characteristic of warfarin. Journal of Education, Health and Sport. 2020;10(8):78-80. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.08.009 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.08.009 https://zenodo.org/record/3969341 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 20.07.2020. Revised: 25.07.2020. Accepted: 01.08.2020. Characteristic of warfarin Marzena Baran1, Paulina Miziak1, Katarzyna Bonio2 1Chair and Department of Biochemistry and Molecular Biology, Medical University of Lublin 2Department of Cell Biology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin Abstract In modern pharmacology, compounds of natural origin are gaining more and more recognition. One of them is warfarin, which is a compound of organic coumarin derivatives. It is used medicinally in the anticoagulant doctor. This compound was commercially introduced to the United States in the 1950s. It has been available on the Polish market since 2006. Warfarin is an antagonist of vitamin K. It works by inhibiting the synthesis of vitamin K in the liver and thus blocking the synthesis of vitamin K dependent blood clotting factors (II, VII, IX, X). It is widely used by people suffering from cardiovascular diseases such as venous thrombosis and venous embolism. Adopted by patients with suspected or after a heart attack. Despite its undisputed positive effect, one should remember about the numerous side effects resulting from long-term use of warfarin. They may be due to intolerance to this compound, which causes nausea, vomiting, and allergic reactions. Moreover, recent studies show that it may have a destructive effect on the liver and cause calcification of blood vessels. Keep in mind that warfarin can interact with many substances you are taking for other medical conditions. Agents that increase the effects of warfarin include antibiotics such as erythromycin, deoxicillin, commonly used drugs containing caffeine, acetylsalicylic acid and naturally derived compounds found in ginkgo, garlic and sage. Compounds that weaken the effect of warfarin are barbiturates, cyclosporine, vitamin C, and St. John's wort. Key words: warfarin, cumarine, vitamin K antagonist, medicine, anticoagulants

The sirtuin family comprises seven NAD+-dependent histone deacetylases named SIRT1 to SIRT7. The least investigated SIRT7 is currently considered as a promising therapeutic target for cardiovascula...

Miziak Paulina, Baran Marzena, Bonio Katarzyna, Piech Piotr. Nanoparticles in medicine. Journal of Education, Health and Sport. 2020;10(8):17-21. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.08.002 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.08.002 https://zenodo.org/record/3967771 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 05.07.2020. Revised: 15.07.2020. Accepted: 30.07.2020. Nanoparticles in medicine Paulina Miziak1, Marzena Baran1, Katarzyna Bonio2, Piotr Piech3 1Chair and Department of Biochemistry and Molecular Biology, Medical University of Lublin 2Department of Cell Biology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Lublin 3Human Anatomy Department, Medical University of Lublin, Poland Abstract Nanotechnology is a new, interdisciplinary field of science, the products of which are nanoparticles, i.e. structures that, thanks to their unique physical and chemical properties conditioned by their nanometric dimensions, have found wide application in medicine, pharmacy and biotechnology. Currently, they play a particularly important role as drug carriers, antibacterial and antiviral substances. They are also used in diagnostics, genetic tests, and increasing the accuracy of biological tests. The enormous possibilities of nanoparticles concern their potential use as drug delivery systems, factors improving the quality of anticancer radiotherapy and supporting molecular imaging, as well as compounds with highly bactericidal, fungicidal and antiviral properties. Therefore, it is crucial to implement therapies based on nanoparticles into clinical trials, as they can be an excellent diagnostic and therapeutic tool for many diseases, including cancer. However, it is necessary to overcome certain barriers due to the nature of some nanoparticles, such as problems with biodegradability and porosity. Despite the benefits of using nanostructures, the possibility of side effects caused by the action of metal nanoparticles absorbed by organisms has not been ruled out. Key words: nanoparticle, medicine, drug delivery, peptide, tissue

Naturally occurring coumarins are bioactive compounds widely used in Asian traditional medicine. They have been shown to inhibit proliferation, induce apoptosis, and/or enhance the cytotoxicity of currently used drugs against a variety of cancer cell types. The aim of our study was to examine the antiproliferative activity of different linear furanocoumarins on human rhabdomyosarcoma, lung, and larynx cancer cell lines, and dissolve their cellular mechanism of action. The coumarins were isolated from fruits of Angelica archangelica L. or Pastinaca sativa L., and separated using high-performance counter-current chromatography (HPCCC). The identity and purity of isolated compounds were confirmed by HPLC-DAD and NMR analyses. Cell viability and toxicity assessments were performed by means of methylthiazolyldiphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. Induction of apoptosis and cell cycle progression were measured using flow cytometry analysis. qPCR method was applied to detect changes in gene expression. Linear furanocoumarins in a dose-dependent manner inhibited proliferation of cancer cells with diverse activity regarding compounds and cancer cell type specificity. Imperatorin (IMP) exhibited the most potent growth inhibitory effects against human rhabdomyosarcoma and larynx cancer cell lines owing to inhibition of the cell cycle progression connected with specific changes in gene expression, including CDKN1A. As there are no specific chemotherapy treatments dedicated to laryngeal squamous cell carcinoma and rhabdomyosarcoma, and IMP seems to be non-toxic for normal cells, our results could open a new direction in the search for effective anti-cancer agents.

The sirtuin family comprises seven NAD

Histone deacetylase inhibitors (HDIs) are a group of potent epigenetic drugs which have been investigated for their therapeutic potential in various clinical disorders, including hematological malignancies and solid tumors. Currently, several HDIs are already in clinical use and many more are on clinical trials. HDIs have shown efficacy to inhibit initiation and progression of cancer cells. Nevertheless, both pro-invasive and anti-invasive activities of HDIs have been reported, questioning their impact in carcinogenesis. The aim of this review is to compile and discuss the most recent findings on the effect of HDIs on the epithelial-mesenchymal transition (EMT) process in human cancers. We have summarized the impact of HDIs on epithelial (E-cadherin, β-catenin) and mesenchymal (N-cadherin, vimentin) markers, EMT activators (TWIST, SNAIL, SLUG, SMAD, ZEB), as well as morphology, migration and invasion potential of cancer cells. We further discuss the use of HDIs as monotherapy or in combination with existing or novel anti-neoplastic drugs in relation to changes in EMT.