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      Anticancer Effects of Wild Mountain Mentha longifolia Extract in Adrenocortical Tumor Cell Models

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          Abstract

          Mint [ Mentha longifolia (L.) Hudson] is an aromatic plant that belongs to Lamiaceae family. It is traditionally used as herbal tea in Europe, Australia and North Africa and shows numerous pharmacological effects, such as spasmolytic, antioxidant, antimicrobial and anti-hemolytic. Recently, its antiproliferative role has been suggested in a small number of tumor cell models, but no data are available on adrenocortical carcinoma, a malignancy with a survival rate at 5 years of 20%–30% which frequently metastasize. This work aimed to study the effects of Mentha longifolia L. crude extract (ME) on two adrenocortical tumor cell models (H295R and SW13 cells). Chemical composition of ME was assessed by gas-chromatography/mass spectrometry and NMR spectroscopy analysis. Brine shrimp lethality assay showed ME effects at >0.5 µg/µl (p < 0.05). Cell viability and vitality were determined by MTT, SRB, and trypan blue assays in H295R and SW13 cells. The anti-proliferative effects of ME were more evident in SW13 cells at 72 h (ME > 0.5 µg/µl, p < 0.05). Combination of ME with mitotane (approved drug for adrenocortical carcinoma) seemed not to reinforce the efficacy of the herb. As control, human fibroblasts were treated with ME with no effect on cell viability. Clonogenic assay was concordant with previous cell viability tests (ME > 0.5 µg/µl, p < 0.05), while Wright staining demonstrated the presence of both necrotic and apoptotic cells. Cell cycle analysis showed a strong increase in subG0/G1 phase, related to cell death. Furthermore, MAPK and PI3k/Akt pathways were modulated by Western blot analysis when treating cells with ME alone or combined with mitotane. The crude methanolic extract of wild mountain mint can decrease cell viability, vitality and survival of adrenocortical tumor cell models, in particular of SW13 cells. These data show the potential anticancer effects of ME, still more work is needed to corroborate these findings.

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          DNA damage and the balance between survival and death in cancer biology.

          DNA is vulnerable to damage resulting from endogenous metabolites, environmental and dietary carcinogens, some anti-inflammatory drugs, and genotoxic cancer therapeutics. Cells respond to DNA damage by activating complex signalling networks that decide cell fate, promoting not only DNA repair and survival but also cell death. The decision between cell survival and death following DNA damage rests on factors that are involved in DNA damage recognition, and DNA repair and damage tolerance, as well as on factors involved in the activation of apoptosis, necrosis, autophagy and senescence. The pathways that dictate cell fate are entwined and have key roles in cancer initiation and progression. Furthermore, they determine the outcome of cancer therapy with genotoxic drugs. Understanding the molecular basis of these pathways is important not only for gaining insight into carcinogenesis, but also in promoting successful cancer therapy. In this Review, we describe key decision-making nodes in the complex interplay between cell survival and death following DNA damage.
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            What is synergy? The Saariselkä agreement revisited

            Many biological or chemical agents when combined interact with each other and produce a synergistic response that cannot be predicted based on the single agent responses alone. However, depending on the postulated null hypothesis of non-interaction, one may end up in different interpretations of synergy. Two popular reference models for null hypothesis include the Bliss independence model and the Loewe additivity model, each of which is formulated from different perspectives. During the last century, there has been an intensive debate on the suitability of these synergy models, both of which are theoretically justified and also in practice supported by different schools of scientists. More than 20 years ago, there was a community effort to make a consensus on the terminology one should use when claiming synergy. The agreement was formulated at a conference held in Saariselkä, Finland in 1992, stating that one should use the terms Bliss synergy or Loewe synergy to avoid ambiguity in the underlying models. We review the theoretical relationships between these models and argue that one should combine the advantages of both models to provide a more consistent definition of synergy and antagonism.
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              Seasonal variation in content, chemical composition and antimicrobial and cytotoxic activities of essential oils from four Mentha species.

              The aim of the present study was to appraise variation in the chemical composition, and antimicrobial and cytotoxic activities of essential oils from the leaves of four Mentha species-M. arvensis, M. piperita, M. longifolia and M. spicata-as affected by harvesting season. Disc diffusion and broth microdilution susceptibility assays were used to evaluate the antimicrobial activity of Mentha essential oils against a panel of microorganisms. The cytotoxicity of essential oils was tested on breast cancer (MCF-7) and prostate cancer (LNCaP) cell lines using the MTT assay. The essential oil contents of M. arvensis, M. piperita, M. longifolia and M. spicata were 17.0, 12.2, 10.8 and 12.0 g kg(-1) from the summer and 9.20, 10.5, 7.00 and 9.50 g kg(-1) from the winter crops, respectively. Gas chromatographic-mass spectrometric analysis revealed that mostly quantitative rather than qualitative variation was observed in the oil composition of each species. The principal chemical constituents determined in M. arvensis, M. piperita, M. longifolia and M. spicata essential oils from both seasons were menthol, menthone, piperitenone oxide and carvone, respectively. The tested essential oils and their major components exhibited notable antimicrobial activity against most of the plant and human pathogens tested. The tested essential oils also exhibited good cytotoxicity potential. Of the Mentha essential oils tested, M. arvensis essential oil showed relatively better antimicrobial and cytotoxic activities. A significant variation in the content of most of the chemical components and biological activities of seasonally collected samples was documented. Copyright (c) 2010 Society of Chemical Industry.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                10 February 2020
                2019
                : 10
                : 1647
                Affiliations
                [1] 1Endocrinology Unit, Department of Medicine (DIMED), University of Padova , Padova, Italy
                [2] 2BioOrgNMR Lab, Department of Biotechnology and Biosciences, Università degli Studi di Milano Bicocca , Milan, Italy
                [3] 3Department of Agricultural and Environmental Sciences, Milan State University , Milano, Italy
                [4] 4AIROB, Associazione Italiana per la Ricerca Oncologica di Base , Padova, Italy
                [5] 5Venetian Institute for Molecular Science and Experimental Technologies, VIMSET , Liettoli di Campolongo Maggiore, Italy
                [6] 6Minimally Invasive Endocrine Surgery Unit, Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova , Padova, Italy
                Author notes

                Edited by: Ilaria Peluso, Council for Agricultural and Economics Research, Italy

                Reviewed by: Muhammad Ayaz, University of Malakand, Pakistan; Teresa Gagliano, University of Sussex, United Kingdom

                *Correspondence: Marcello Iriti, marcello.iriti@ 123456unimi.it ; Raffaele Pezzani, raffaele.pezzani@ 123456unipd.it

                This article was submitted to Inflammation Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2019.01647
                7025550
                6944fa69-a10b-4120-9753-661b37b4d4b2
                Copyright © 2020 Patti, Palmioli, Vitalini, Bertazza, Redaelli, Zorzan, Rubin, Mian, Bertolini, Iacobone, Armanini, Barollo, Airoldi, Iriti and Pezzani

                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
                : 24 June 2019
                : 16 December 2019
                Page count
                Figures: 7, Tables: 1, Equations: 0, References: 52, Pages: 11, Words: 5559
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                mentha longifolia,mint,adrenocortical carcinoma,cell assay,cell models,phytotherapy

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