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      Histone deacetylases modulate resistance to the therapy in lung cancer

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          Abstract

          The acetylation status of histones located in both oncogenes and tumor suppressor genes modulate cancer hallmarks. In lung cancer, changes in the acetylation status are associated with increased cell proliferation, tumor growth, migration, invasion, and metastasis. Histone deacetylases (HDACs) are a group of enzymes that take part in the elimination of acetyl groups from histones. Thus, HDACs regulate the acetylation status of histones. Although several therapies are available to treat lung cancer, many of these fail because of the development of tumor resistance. One mechanism of tumor resistance is the aberrant expression of HDACs. Specific anti-cancer therapies modulate HDACs expression, resulting in chromatin remodeling and epigenetic modification of the expression of a variety of genes. Thus, HDACs are promising therapeutic targets to improve the response to anti-cancer treatments. Besides, natural compounds such as phytochemicals have potent antioxidant and chemopreventive activities. Some of these compounds modulate the deregulated activity of HDACs (e.g. curcumin, apigenin, EGCG, resveratrol, and quercetin). These phytochemicals have been shown to inhibit some of the cancer hallmarks through HDAC modulation. The present review discusses the epigenetic mechanisms by which HDACs contribute to carcinogenesis and resistance of lung cancer cells to anticancer therapies.

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          Most cited references125

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Curcumin: A Review of Its’ Effects on Human Health

            Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.
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              Erasers of histone acetylation: the histone deacetylase enzymes.

              Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl functional groups from the lysine residues of both histone and nonhistone proteins. In humans, there are 18 HDAC enzymes that use either zinc- or NAD(+)-dependent mechanisms to deacetylate acetyl lysine substrates. Although removal of histone acetyl epigenetic modification by HDACs regulates chromatin structure and transcription, deacetylation of nonhistones controls diverse cellular processes. HDAC inhibitors are already known potential anticancer agents and show promise for the treatment of many diseases.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                03 October 2022
                2022
                : 13
                : 960263
                Affiliations
                [1] 1 Posgrado de Ciencias Genómicas , Universidad Autónoma de la Ciudad de México , Ciudad de México, México
                [2] 2 Laboratorio de Onco-Inmunobiologia , Departamento de Enfermedades Crónico-Degenerativas , Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas , Ciudad de México, México
                [3] 3 Facultad de Ciencias , Universidad Nacional Autónoma de México , Ciudad de México, México
                [4] 4 Departamento de Investigación en Bioquímica , Unidad de Investigación , Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas , Ciudad de México, México
                [5] 5 Servicio de Patología , Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas , Ciudad de México, México
                [6] 6 Laboratorio de Biología Molecular , Instituto Nacional de Pediatría , Ciudad de México, México
                Author notes

                Edited by: Rui Henrique, Portuguese Oncology Institute, Portugal

                Reviewed by: Biswa Prasun Chatterji, Ajeenkya D Y Patil University, India

                Jian Liu, Nanjing University of Chinese Medicine, China

                Yingjie Zhang, Shandong University, China

                A. Ganesan, University of East Anglia, United Kingdom

                *Correspondence: Ángeles Carlos-Reyes, reyes_cardoso@ 123456yahoo.com

                This article was submitted to Cancer Genetics and Oncogenomics, a section of the journal Frontiers in Genetics

                Article
                960263
                10.3389/fgene.2022.960263
                9574126
                36263432
                523ec1d9-9c11-496c-80b5-09bc827de69e
                Copyright © 2022 Contreras-Sanzón, Prado-Garcia, Romero-Garcia, Nuñez-Corona, Ortiz-Quintero, Luna-Rivero, Martínez-Cruz and Carlos-Reyes.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 June 2022
                : 07 September 2022
                Funding
                Funded by: Consejo Nacional de Ciencia y Tecnología , doi 10.13039/501100003141;
                Categories
                Genetics
                Review

                Genetics
                lung cancer,histone deacetylases (hdacs),hdacs inhibitors,resistance to therapy,natural compounds

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