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      Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential

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          Abstract

          Despite advancements in healthcare facilities for diagnosis and treatment, cancer remains the leading cause of death worldwide. As prevention is always better than cure, efficient strategies are needed in order to deal with the menace of cancer. The use of phytochemicals as adjuvant chemotherapeutic agents in heterogeneous human carcinomas like breast, colon, lung, ovary, and prostate cancers has shown an upward trend during the last decade or so. Flavonoids are well-known products of plant derivatives that are reportedly documented to be therapeutically active phytochemicals against many diseases encompassing malignancies, inflammatory disorders (cardiovascular disease, neurodegenerative disorder), and oxidative stress. The current review focuses on two key flavonols, fisetin and quercetin, known for their potential pharmacological relevance. Also, efforts have been made to bring together most of the concrete studies pertaining to the bioactive potential of fisetin and quercetin, especially in the modulation of a range of cancer signaling pathways. Further emphasis has also been made to highlight the molecular action of quercetin and fisetin so that one could explore cancer initiation pathways and progression, which could be helpful in designing effective treatment strategies.

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          Most cited references170

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          Targeted cancer therapy.

          Disruption of the normal regulation of cell-cycle progression and division lies at the heart of the events leading to cancer. Complex networks of regulatory factors, the tumour microenvironment and stress signals, such as those resulting from damaged DNA, dictate whether cancer cells proliferate or die. Recent progress in understanding the molecular changes that underlie cancer development offer the prospect of specifically targeting malfunctioning molecules and pathways to achieve more effective and rational cancer therapy.
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            Exosome-Mediated Metastasis: From Epithelial-Mesenchymal Transition to Escape from Immunosurveillance.

            Exosomes are extracellular signalosomes that facilitate eukaryotic intercellular communication under a wide range of normal physiological contexts. In malignancies, this regulatory circuit is co-opted to promote cancer cell survival and outgrowth. Tumour-derived exosomes (TDEs) carry a pro-EMT (epithelial-mesenchymal transition) programme including transforming growth factor beta (TGFβ), caveolin-1, hypoxia-inducible factor 1 alpha (HIF1α), and β-catenin that enhances the invasive and migratory capabilities of recipient cells, and contributes to stromal remodelling and premetastatic niche formation. The integrin expression patterns on TDEs appear to dictate their preferential uptake by organ-specific cells, implying a crucial role of this pathway in organotropic metastasis. Through the expression of immunomodulatory molecules such as CD39 and CD73, TDEs modify the immune contexture of the tumour microenvironment, which could have implications for immunotherapy. Hence, targeting TDE dysregulation pathways, such as the heparanase/syndecan-1 axis, could represent novel therapeutic strategies in the quest to conquer cancer.
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              Induction of apoptosis by cancer chemotherapy.

              Studies performed over the past five years have demonstrated that there are two major cell-intrinsic pathways for inducing apoptosis, one that begins with ligation of cell surface death receptors and another that involves mitochondrial release of cytochrome c. Several reports have suggested that anticancer drugs kill susceptible cells by inducing expression of death receptor ligands, especially Fas ligand (FasL). Other reports have indicated that chemotherapeutic agents trigger apoptosis by inducing release of cytochrome c from mitochondria. In this review, we describe the two prototypic death pathways, indicate experimental approaches for distinguishing whether chemotherapeutic agents trigger one pathway or the other, summarize current understanding of the role of the two pathways in chemotherapy-induced apoptosis, and discuss the implications of these studies for mechanisms of resistance to chemotherapeutic agents. Copyright 2000 Academic Press.
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                Author and article information

                Journal
                Biomolecules
                Biomolecules
                biomolecules
                Biomolecules
                MDPI
                2218-273X
                06 May 2019
                May 2019
                : 9
                : 5
                : 174
                Affiliations
                [1 ]Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, Punjab, India; make.must@ 123456gmail.com (D.K.); vaishali.pgi@ 123456gmail.com (V.A.)
                [2 ]Department of Biochemistry, Government Medical College and Hospital (GMCH), Chandigarh 160031, Punjab, India; garg.vivek85@ 123456gmail.com
                [3 ]Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala 133 207, Haryana, India; anibiotech18@ 123456gmail.com
                [4 ]Department of Pharmacology, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Turkey; eczbetul@ 123456yahoo.com
                [5 ]NGO Praeventio, Tartu 50407, Estonia; katrin.sak.001@ 123456mail.ee
                [6 ]Department of Chemistry, Maharishi Markandeshwar University, Sadopur 134007, Haryana, India; Manojraju27@ 123456gmail.com
                [7 ]Department of Biological Sciences, RD University, Jabalpur 482001, India; sardulsinghsandhu@ 123456gmail.com
                Author notes
                [* ]Correspondence: hardeep.biotech@ 123456gmail.com ; Tel.: +91-9896619923
                Author information
                https://orcid.org/0000-0002-4503-8032
                https://orcid.org/0000-0003-0736-2525
                Article
                biomolecules-09-00174
                10.3390/biom9050174
                6572624
                31064104
                53b9a29a-e0b1-4061-8d45-a6d1d9987bbc
                © 2019 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
                : 02 April 2019
                : 30 April 2019
                Categories
                Review

                apoptosis,cell cycle arrest,extracellular matrix remodeling,epithelial to mesenchymal transition,signaling cascades,flavonoids,fisetin,quercetin

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