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      Potential Therapeutic Targets of Quercetin, a Plant Flavonol, and Its Role in the Therapy of Various Types of Cancer through the Modulation of Various Cell Signaling Pathways


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          Polyphenolic flavonoids are considered natural, non-toxic chemopreventers, which are most commonly derived from plants, fruits, and vegetables. Most of these polyphenolics exhibit remarkable antioxidant, anti-inflammatory, and anticancer properties. Quercetin (Qu) is a chief representative of these polyphenolic compounds, which exhibits excellent antioxidant and anticancer potential, and has attracted the attention of researchers working in the area of cancer biology. Qu can regulate numerous tumor-related activities, such as oxidative stress, angiogenesis, cell cycle, tumor necrosis factor, proliferation, apoptosis, and metastasis. The anticancer properties of Qu mainly occur through the modulation of vascular endothelial growth factor (VEGF), apoptosis, phosphatidyl inositol-3-kinase (P13K)/Akt (proteinase-kinase B)/mTOR (mammalian target of rapamycin), MAPK (mitogen activated protein kinase)/ERK1/2 (extracellular signal-regulated kinase 1/2), and Wnt/β-catenin signaling pathways. The anticancer potential of Qu is documented in numerous in vivo and in vitro studies, involving several animal models and cell lines. Remarkably, this phytochemical possesses toxic activities against cancerous cells only, with limited toxic effects on normal cells. In this review, we present extensive research investigations aimed to discuss the therapeutic potential of Qu in the management of different types of cancers. The anticancer potential of Qu is specifically discussed by focusing its ability to target specific molecular signaling, such as p53, epidermal growth factor receptor (EGFR), VEGF, signal transducer and activator of transcription (STAT), PI3K/Akt, and nuclear factor kappa B (NF- κB) pathways. The anticancer potential of Qu has gained remarkable interest, but the exact mechanism of its action remains unclear. However, this natural compound has great pharmacological potential; it is now believed to be a complementary—or alternative—medicine for the prevention and treatment of different cancers.

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Hallmarks of Cancer: The Next Generation

            The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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              The Hallmarks of Cancer


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                Role: Academic Editor
                Role: Academic Editor
                Role: Academic Editor
                01 March 2021
                March 2021
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                [1 ]Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51542, Saudi Arabia; smtrody@ 123456qu.edu.sa (S.A.A.); shly@ 123456qu.edu.sa (M.A.A.); aamtrody@ 123456qu.edu.sa (A.A.); k.allemailem@ 123456qu.edu.sa (K.S.A.)
                [2 ]Department of Biotechnology, Jamia Millia Islamia, New Delhi 51542, India; amitvrm999@ 123456gmail.com
                [3 ]Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraydah 51542, Saudi Arabia; aaalieky@ 123456qu.edu.sa
                [4 ]Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51542, Saudi Arabia; akhan@ 123456qu.edu.sa
                Author notes
                [* ]Correspondence: ah.rahmani@ 123456qu.edu.sa
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                © 2021 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/).

                : 23 January 2021
                : 25 February 2021

                quercetin,polyphenolic flavonoids,natural chemopreventers,cell signaling pathways,anticancer activity,bioavailability


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