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      Anticancer Activity of Rosmarinus officinalis L.: Mechanisms of Action and Therapeutic Potentials

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          Abstract

          Alternative treatments for neoplastic diseases with new drugs are necessary because the clinical effectiveness of chemotherapy is often reduced by collateral effects. Several natural substances of plant origin have been demonstrated to be successful in the prevention and treatment of numerous tumors. Rosmarinus officinalis L. is a herb that is cultivated in diverse areas of the world. There is increasing attention being directed towards the pharmaceutical capacities of rosemary, utilized for its anti-inflammatory, anti-infective or anticancer action. The antitumor effect of rosemary has been related to diverse mechanisms, such as the antioxidant effect, antiangiogenic properties, epigenetic actions, regulation of the immune response and anti-inflammatory response, modification of specific metabolic pathways, and increased expression of onco-suppressor genes. In this review, we aim to report the results of preclinical studies dealing with the anticancer effects of rosemary, the molecular mechanisms related to these actions, and the interactions between rosemary and anticancer drugs. The prospect of utilizing rosemary as an agent in the treatment of different neoplastic diseases is discussed. However, although the use of rosemary in the therapy of neoplasms constitutes a fascinating field of study, large and controlled studies must be conducted to definitively clarify the real impact of this substance in clinical practice.

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          Most cited references137

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          Inflammation as a tumor promoter in cancer induction.

          Opposing effects of inflammation on cancer have been described. Acute inflammation usually counteracts cancer development, while chronic inflammation promotes cancer development. Just as inactivation of the p53 pathway may be universal in the neoplasia, the activation of the NFkappaB pathway may, conversely, be frequent in carcinogenesis, and a requirement for inflammation and promotion. TNF, a key pro-inflammatory cytokine when binding to TNF receptor 1 (TNFR1), may cause survival or apoptosis, dependent on biochemical modifications that determine the type of complex formed; one complex causes NFkappaB activation and gives a cell survival signal (pro-oncogenic), while the other (modified) complex recruits caspases and causes apoptosis (anti-oncogenic). Fas-ligand (FasL)-Fas interaction can also result in opposing effects on carcinogenesis due to similar mechanisms. While IL-6 counteracts apoptosis and can promote cancer development, interferons can increase DNA repair and stabilize p53, thereby be anti-oncogenic.
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            Oral Cancer and Precancerous Lesions

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              To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis.

              During their lifetime, cells encounter many life or death situations that challenge their very own existence. Their survival depends on the interplay within a complex yet precisely orchestrated network of proteins. The Rel/NF-kappaB signaling pathway and the transcription factors that it activates have emerged as critical regulators of the apoptotic response. These proteins are best known for the key roles that they play in normal immune and inflammatory responses, but they are also implicated in the control of cell proliferation, differentiation, apoptosis and oncogenesis. In recent years, there has been remarkable progress in understanding the pathways that activate the Rel/NF-kappaB factors and their role in the cell's decision to either fight or surrender to apoptotic challenge. Whereas NF-kappaB is most commonly involved in suppressing apoptosis by transactivating the expression of antiapoptotic genes, it can promote programmed cell death in response to certain death-inducing signals and in certain cell types. This review surveys our current understanding of the role of NF-kappaB in the apoptotic response and focuses on many developments since this topic was last reviewed in Oncogene 4 years ago. These recent findings shed new light on the activity of NF-kappaB as a critical regulator of apoptosis in the immune, hepatic, epidermal and nervous systems, on the mechanisms through which it operates and on its role in tissue development, homoeostasis and cancer.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                10 June 2020
                June 2020
                : 12
                : 6
                : 1739
                Affiliations
                [1 ]Division of Haematology, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, 98125 Messina, Italy; cmusolino@ 123456unime.it
                [2 ]Clinical Physiology Institute, National Research Council of Italy (IFC-CNR), 56124 Pisa, Italy; atonacci@ 123456ifc.cnr.it
                [3 ]Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), 98164 Messina, Italy; giovanni.pioggia@ 123456cnr.it
                [4 ]School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; gangemis@ 123456unime.it
                Author notes
                [* ]Correspondence: aallegra@ 123456unime.it
                Author information
                https://orcid.org/0000-0001-6156-8239
                https://orcid.org/0000-0001-8335-5541
                Article
                nutrients-12-01739
                10.3390/nu12061739
                7352773
                32532056
                8980d135-ec6d-4acb-815e-d7ce41745e64
                © 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
                : 06 May 2020
                : 08 June 2020
                Categories
                Review

                Nutrition & Dietetics
                rosmarinus officinalis l.,rosemary,carnosic acid,carnosol,cancer,leukemia,chemoresistance,synergistic effect

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