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      Apple pectin-based Zataria multiflora essential oil (ZEO) nanoemulsion: An approach to enhance ZEO DNA damage induction in breast cancer cells as in vitro and in silico studies reveal

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          Abstract

          Zataria multiflora essential oil (ZEO) is a natural complex of compounds with a high apoptotic potential against breast cancer cells and minor toxicity toward normal cells; however, similar to many essential oils, ZEO utilization in pharmaceutical industries has limitations due to its labile and sensitive ingredients. Nanoemulsification based on natural polymers is one approach to overcome this issue. In this study, an apple pectin-ZEO nanoemulsion (AP-ZEONE) was prepared and its morphology, FTIR spectra, and physical properties were characterized. Furthermore, it was shown that AP-ZEONE substantially suppresses the viability of MDA-MB-231, T47D, and MCF-7 breast cancer cells. AP-ZEONE significantly induced apoptotic morphological alterations and DNA fragmentation as confirmed by fluorescent staining and TUNEL assay. Moreover, AP-ZEONE induced apoptosis in MDA-MB-231 cells by loss of mitochondrial membrane potential (ΔΨm) associated with the accumulation of reactive oxygen species (ROS), G2/M cell cycle arrest, and DNA strand breakage as flow cytometry, DNA oxidation, and comet assay analysis revealed, respectively. Spectroscopic and computational studies also confirmed that AP-ZEONE interacts with genomic DNA in a minor groove/partial intercalation binding mode. This study demonstrated the successful inhibitory effect of AP-ZEONE on metastatic breast cancer cells, which may be beneficial in the therapy process.

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          Most cited references33

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          Activation of apoptosis signalling pathways by reactive oxygen species.

          Reactive oxygen species (ROS) are short-lived and highly reactive molecules. The generation of ROS in cells exists in equilibrium with a variety of antioxidant defences. At low to modest doses, ROS are considered to be essential for regulation of normal physiological functions involved in development such as cell cycle progression and proliferation, differentiation, migration and cell death. ROS also play an important role in the immune system, maintenance of the redox balance and have been implicated in activation of various cellular signalling pathways. Excess cellular levels of ROS cause damage to proteins, nucleic acids, lipids, membranes and organelles, which can lead to activation of cell death processes such as apoptosis. Apoptosis is a highly regulated process that is essential for the development and survival of multicellular organisms. These organisms often need to discard cells that are superfluous or potentially harmful, having accumulated mutations or become infected by pathogens. Apoptosis features a characteristic set of morphological and biochemical features whereby cells undergo a cascade of self-destruction. Thus, proper regulation of apoptosis is essential for maintaining normal cellular homeostasis. ROS play a central role in cell signalling as well as in regulation of the main pathways of apoptosis mediated by mitochondria, death receptors and the endoplasmic reticulum (ER). This review focuses on current understanding of the role of ROS in each of these three main pathways of apoptosis. The role of ROS in the complex interplay and crosstalk between these different signalling pathways remains to be further unravelled during the coming years.
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            Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent.

            Non-structural phenolic compounds perform a variety of functions in plants, including acting as antioxidants. We describe a microplate-adapted colorimetric total phenolics assay that utilizes Folin-Ciocalteu (F-C) reagent. The F-C assay relies on the transfer of electrons in alkaline medium from phenolic compounds to phosphomolybdic/phosphotungstic acid complexes, which are determined spectroscopically at 765 nm. Although the electron transfer reaction is not specific for phenolic compounds, the extraction procedure eliminates approximately 85% of ascorbic acid and other potentially interfering compounds. This assay is performed in microcentrifuge tubes and assessed in a 96-well plate reader. At least 64 samples can be processed in 1 d.
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              Natural products in cancer chemotherapy: past, present and future.

              John Mann (2002)
              Natural products have been the mainstay of cancer chemotherapy for the past 30 years. However, the quickening pace of (aberrant) gene identification, and the new technologies of combinatorial chemistry and high-throughput screening, should provide access to a wide range of new, totally synthetic drugs. Will these new approaches sound the death knell for therapies based on natural products? In reality, natural products are likely to provide many of the lead structures, and these will be used as templates for the construction of novel compounds with enhanced biological properties.
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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
                05 September 2022
                2022
                : 13
                : 946161
                Affiliations
                [ 1 ] Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran , Tehran, Iran
                [ 2 ] Faculty of Biology, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University , Tehran, Iran
                [ 3 ] Tehran Medical sciences, Islamic Azad University , Tehran, Iran
                [ 4 ] Department of Microbiology, College of Science, University of Tehran , Tehran, Iran
                [ 5 ] Institute of Biotechnology, Shiraz University , Shiraz, Iran
                Author notes
                *Correspondence: Gholamreza Kavoosi, kavoosi.gholamreza@ 123456yahoo.com

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

                Edited by: Yiqun Deng, South China Agricultural University, China

                Reviewed by: Mohammad Reza Khazdair, Birjand University of Medical Sciences, Iran

                Ehsan Karimi, Islamic Azad University of Mashhad, Iran

                Article
                946161
                10.3389/fphar.2022.946161
                9483017
                5ca00f31-bf3e-46e6-a85f-3fdadcdf920a
                Copyright © 2022 Salehi, Behboudi, Salehi, Ardestani, Piroozmand and Kavoosi.

                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
                : 01 June 2022
                : 18 July 2022
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                apple pectin, zataria multiflora essential oil,nanoemulsion,breast cancer,apoptosis,dna damage

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