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      Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

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          Abstract

          Simple Summary

          In the last years, targeted therapy and immunotherapy modified the landscape for metastatic melanoma treatment. These therapeutic approaches led to an impressive improvement in patients overall survival. Unfortunately, the emergence of drug resistance and side effects occurring during therapy strongly limit the long-term efficacy of such treatments. Several preclinical studies demonstrate the efficacy of essential oils as antitumoral agents, and clinical trials support their use to reduce side effects emerging during therapy. In this review we have summarized studies describing the molecular mechanism through which essential oils induce in vitro and in vivo cell death in melanoma models. We also pointed to clinical trials investigating the use of essential oils in reducing the side effects experienced by cancer patients or those undergoing anticancer therapy. From this review emerged that further studies are necessary to validate the effectiveness of essential oils for the management of melanoma.

          Abstract

          The last two decades have seen the development of effective therapies, which have saved the lives of a large number of melanoma patients. However, therapeutic options are still limited for patients without BRAF mutations or in relapse from current treatments, and severe side effects often occur during therapy. Thus, additional insights to improve treatment efficacy with the aim to decrease the likelihood of chemoresistance, as well as reducing side effects of current therapies, are required. Natural products offer great opportunities for the discovery of antineoplastic drugs, and still represent a useful source of novel molecules. Among them, essential oils, representing the volatile fraction of aromatic plants, are always being actively investigated by several research groups and show promising biological activities for their use as complementary or alternative medicine for several diseases, including cancer. In this review, we focused on studies reporting the mechanism through which essential oils exert antitumor action in preclinical wild type or mutant BRAF melanoma models. We also discussed the latest use of essential oils in improving cancer patients’ quality of life. As evidenced by the many studies listed in this review, through their effect on apoptosis and tumor progression-associated properties, essential oils can therefore be considered as potential natural pharmaceutical resources for cancer management.

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          Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

          Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.
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            Cell death: a review of the major forms of apoptosis, necrosis and autophagy

            Cell death was once believed to be the result of one of two distinct processes, apoptosis (also known as programmed cell death) or necrosis (uncontrolled cell death); in recent years, however, several other forms of cell death have been discovered highlighting that a cell can die via a number of differing pathways. Apoptosis is characterised by a number of characteristic morphological changes in the structure of the cell, together with a number of enzyme-dependent biochemical processes. The result being the clearance of cells from the body, with minimal damage to surrounding tissues. Necrosis, however, is generally characterised to be the uncontrolled death of the cell, usually following a severe insult, resulting in spillage of the contents of the cell into surrounding tissues and subsequent damage thereof. Failure of apoptosis and the resultant accumulation of damaged cells in the body can result in various forms of cancer. An understanding of the pathways is therefore important in developing efficient chemotherapeutics. It has recently become clear that there exists a number of subtypes of apoptosis and that there is an overlap between apoptosis, necrosis and autophagy. The goal of this review is to provide a general overview of the current knowledge relating to the various forms of cell death, including apoptosis, necrosis, oncosis, pyroptosis and autophagy. This will provide researchers with a summary of the major forms of cell death and allow them to compare and contrast between them.
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              An overview of autophagy: morphology, mechanism, and regulation.

              Autophagy is a highly conserved eukaryotic cellular recycling process. Through the degradation of cytoplasmic organelles, proteins, and macromolecules, and the recycling of the breakdown products, autophagy plays important roles in cell survival and maintenance. Accordingly, dysfunction of this process contributes to the pathologies of many human diseases. Extensive research is currently being done to better understand the process of autophagy. In this review, we describe current knowledge of the morphology, molecular mechanism, and regulation of mammalian autophagy. At the mechanistic and regulatory levels, there are still many unanswered questions and points of confusion that have yet to be resolved. Through further research, a more complete and accurate picture of the molecular mechanism and regulation of autophagy will not only strengthen our understanding of this significant cellular process, but will aid in the development of new treatments for human diseases in which autophagy is not functioning properly.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                16 September 2020
                September 2020
                : 12
                : 9
                : 2650
                Affiliations
                [1 ]Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy
                [2 ]Department of Chemistry and Technologies of Drugs, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy; stefania.garzoli@ 123456uniroma1.it (S.G.); rino.ragno@ 123456uniroma1.it (R.R.)
                [3 ]Rome Center for Molecular Design, Department of Drug Chemistry and Technology, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy
                Author notes
                [* ]Correspondence: marta.dimartile@ 123456ifo.gov.it (M.D.M.); donatella.delbufalo@ 123456ifo.gov.it (D.D.B.); Tel.: +39-0652666891 (M.D.M.); +39-0652662575 (D.D.B.)
                Author information
                https://orcid.org/0000-0001-9924-9022
                https://orcid.org/0000-0001-8535-0533
                https://orcid.org/0000-0001-5399-975X
                https://orcid.org/0000-0002-3148-6096
                Article
                cancers-12-02650
                10.3390/cancers12092650
                7565555
                32948083
                31856393-c011-4ae1-afe6-523cc2b2c47a
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 July 2020
                : 14 September 2020
                Categories
                Review

                melanoma,essential oils,angiogenesis,apoptosis,metastasis
                melanoma, essential oils, angiogenesis, apoptosis, metastasis

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