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      Cytotoxic Effects of Plant Sap-Derived Extracellular Vesicles on Various Tumor Cell Types

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          Abstract

          Edible plants have been widely used in traditional therapeutics because of the biological activities of their natural ingredients, including anticancer, antioxidant, and anti-inflammatory properties. Plant sap contains such medicinal substances and their secondary metabolites provide unique chemical structures that contribute to their therapeutic efficacy. Plant extracts are known to contain a variety of extracellular vesicles (EVs) but the effects of such EVs on various cancers have not been investigated. Here, we extracted EVs from four plants— Dendropanax morbifera, Pinus densiflora, Thuja occidentalis, and Chamaecyparis obtusa—that are known to have cytotoxic effects. We evaluated the cytotoxic effects of these EVs by assessing their ability to selectively reduce the viability of various tumor cell types compared with normal cells and low metastatic cells. EVs from D. morbifera and P. densiflora sap showed strong cytotoxic effects on tumor cells, whereas those from T. occidentalis and C. obtusa had no significant effect on any tumor cell types. We also identified synergistic effect of EVs from D. morbifera and P. densiflora saps on breast and skin tumor cells and established optimized treatment concentrations. Our findings suggest these EVs from plant sap as new candidates for cancer treatment.

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          Most cited references55

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          DLS and zeta potential - What they are and what they are not?

          Adequate characterization of NPs (nanoparticles) is of paramount importance to develop well defined nanoformulations of therapeutic relevance. Determination of particle size and surface charge of NPs are indispensable for proper characterization of NPs. DLS (dynamic light scattering) and ZP (zeta potential) measurements have gained popularity as simple, easy and reproducible tools to ascertain particle size and surface charge. Unfortunately, on practical grounds plenty of challenges exist regarding these two techniques including inadequate understanding of the operating principles and dealing with critical issues like sample preparation and interpretation of the data. As both DLS and ZP have emerged from the realms of physical colloid chemistry - it is difficult for researchers engaged in nanomedicine research to master these two techniques. Additionally, there is little literature available in drug delivery research which offers a simple, concise account on these techniques. This review tries to address this issue while providing the fundamental principles of these techniques, summarizing the core mathematical principles and offering practical guidelines on tackling commonly encountered problems while running DLS and ZP measurements. Finally, the review tries to analyze the relevance of these two techniques from translatory perspective.
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            Incidence and Mortality and Epidemiology of Breast Cancer in the World.

            Breast cancer is the most common malignancy in women around the world. Information on the incidence and mortality of breast cancer is essential for planning health measures. This study aimed to investigate the incidence and mortality of breast cancer in the world using age-specific incidence and mortality rates for the year 2012 acquired from the global cancer project (GLOBOCAN 2012) as well as data about incidence and mortality of the cancer based on national reports. It was estimated that 1,671,149 new cases of breast cancer were identified and 521,907 cases of deaths due to breast cancer occurred in the world in 2012. According to GLOBOCAN, it is the most common cancer in women, accounting for 25.1% of all cancers. Breast cancer incidence in developed countries is higher, while relative mortality is greatest in less developed countries. Education of women is suggested in all countries for early detection and treatment. Plans for the control and prevention of this cancer must be a high priority for health policy makers; also, it is necessary to increase awareness of risk factors and early detection in less developed countries.
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              Do nanoparticles present ecotoxicological risks for the health of the aquatic environment?

              M Moore (2006)
              Nanotechnology is a major innovative scientific and economic growth area, which may present a variety of hazards for environmental and human health. The surface properties and very small size of nanoparticles and nanotubes provide surfaces that may bind and transport toxic chemical pollutants, as well as possibly being toxic in their own right by generating reactive radicals. There is a wealth of evidence for the harmful effects of nanoscale combustion-derived particulates (ultrafines), which when inhaled can cause a number of pulmonary pathologies in mammals and humans. However, release of manufactured nanoparticles into the aquatic environment is largely an unknown. This review addresses the possible hazards associated with nanomaterials and harmful effects that may result from exposure of aquatic animals to nanoparticles. Possible nanoparticle association with naturally occurring colloids and particles is considered together with how this could affect their bioavailability and uptake into cells and organisms. Uptake by endocytotic routes are identified as probable major mechanisms of entry into cells; potentially leading to various types of toxic cell injury. The higher level consequences for damage to animal health, ecological risk and possible food chain risks for humans are also considered based on known behaviours and toxicities for inhaled and ingested nanoparticles in the terrestrial environment. It is concluded that a precautionary approach is required with individual evaluation of new nanomaterials for risk to the health of the environment. Although current toxicity testing protocols should be generally applicable to identify harmful effects associated with nanoparticles, research into new methods is required to address the special properties of nanomaterials.
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                Author and article information

                Journal
                J Funct Biomater
                J Funct Biomater
                jfb
                Journal of Functional Biomaterials
                MDPI
                2079-4983
                02 April 2020
                June 2020
                : 11
                : 2
                : 22
                Affiliations
                [1 ]Department of Integrative Biosciences, University of Brain Education, Cheonan 31228, Korea; kimini1127@ 123456naver.com (K.K.); hyeju_yoo@ 123456naver.com (H.J.Y.); skin09_@ 123456naver.com (R.L.)
                [2 ]Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34051, Korea; jjhan@ 123456kaist.ac.kr (J.-H.J.); jihopark@ 123456kaist.ac.kr (J.-H.P.)
                [3 ]Electron Microscopy Research Center, Korea Basic Science Institute, Cheongju 28119, Korea; jaekyung.hyun@ 123456oist.jp
                [4 ]School of Integrative Engineering, Chung-Ang University, Seoul 06911, Korea; blisszen@ 123456lile.cau.ac.kr
                Author notes
                [* ]Correspondence: jhyeon@ 123456ube.ac.kr ; Tel.: +82-41-529-2621; Fax: +82-41-529-2674
                Author information
                https://orcid.org/0000-0002-9595-5496
                Article
                jfb-11-00022
                10.3390/jfb11020022
                7353476
                32252412
                20124706-7fbf-4129-ac25-5f3da6407640
                © 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
                : 11 February 2020
                : 20 March 2020
                Categories
                Article

                plant sap,extracellular vesicles,cytotoxic effects,selective toxicity,synergistic effect

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