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      Targeting the JAK/STAT Signaling Pathway Using Phytocompounds for Cancer Prevention and Therapy

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          Abstract

          Cancer is a prevalent cause of mortality around the world. Aberrated activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway promotes tumorigenesis. Natural agents, including phytochemicals, exhibit potent anticancer activities via various mechanisms. However, the therapeutic potency of phytoconstituents as inhibitors of JAK/STAT signaling against cancer has only come into focus in recent days. The current review highlights phytochemicals that can suppress the JAK/STAT pathway in order to impede cancer cell growth. Various databases, such as PubMed, ScienceDirect, Web of Science, SpringerLink, Scopus, and Google Scholar, were searched using relevant keywords. Once the authors were in agreement regarding the suitability of a study, a full-length form of the relevant article was obtained, and the information was gathered and cited. All the complete articles that were incorporated after the literature collection rejection criteria were applied were perused in-depth and material was extracted based on the importance, relevance, and advancement of the apprehending of the JAK/STAT pathway and their relation to phytochemicals. Based on the critical and comprehensive analysis of literature presented in this review, phytochemicals from diverse plant origins exert therapeutic and cancer preventive effects, at least in part, through regulation of the JAK/STAT pathway. Nevertheless, more preclinical and clinical research is necessary to completely comprehend the capability of modulating JAK/STAT signaling to achieve efficient cancer control and treatment.

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          Most cited references208

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          Cancer Statistics, 2008

          Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,437,180 new cancer cases and 565,650 deaths from cancer are projected to occur in the United States in 2008. Notable trends in cancer incidence and mortality include stabilization of incidence rates for all cancer sites combined in men from 1995 through 2004 and in women from 1999 through 2004 and a continued decrease in the cancer death rate since 1990 in men and since 1991 in women. Overall cancer death rates in 2004 compared with 1990 in men and 1991 in women decreased by 18.4% and 10.5%, respectively, resulting in the avoidance of over a half million deaths from cancer during this time interval. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. Although much progress has been made in reducing mortality rates, stabilizing incidence rates, and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.
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            Cancer chemoprevention with dietary phytochemicals.

            Chemoprevention refers to the use of agents to inhibit, reverse or retard tumorigenesis. Numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents, but attention has recently been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals.
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              NRF2 and cancer: the good, the bad and the importance of context.

              Many studies of chemopreventive drugs have suggested that their beneficial effects on suppression of carcinogenesis and many other chronic diseases are mediated through activation of the transcription factor NFE2-related factor 2 (NRF2). More recently, genetic analyses of human tumours have indicated that NRF2 may conversely be oncogenic and cause resistance to chemotherapy. It is therefore controversial whether the activation, or alternatively the inhibition, of NRF2 is a useful strategy for the prevention or treatment of cancer. This Opinion article aims to rationalize these conflicting perspectives by critiquing the context dependence of NRF2 functions and the experimental methods behind these conflicting data.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                11 June 2020
                June 2020
                : 9
                : 6
                : 1451
                Affiliations
                [1 ]Department of Pharmacognosy, Bengal School of Technology, Chuchura 712 102, India; sankha.bose@ 123456gmail.com
                [2 ]Department of Phytochemistry, Gupta College of Technological Sciences, Asansol 713 301, India; sabyasachibanerjee04@ 123456gmail.com (S.B.); utsabcky@ 123456gmail.com (U.C.)
                [3 ]Department of Pharmaceutical Chemistry, Bengal College of Pharmaceutical Technology, Dubrajpur 731 123, India
                [4 ]Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA; JPumarol36499@ 123456med.lecom.edu (J.P.); CCroley48578@ 123456med.lecom.edu (C.R.C.)
                Author notes
                [* ]Correspondence: juarijitmondal@ 123456gmail.com (A.M.); abishayee@ 123456lecom.edu or abishayee@ 123456gmail.com (A.B.); Tel.: +91-967-412-4916 (A.M.); +1-941-782-5950 (A.B.)
                Author information
                https://orcid.org/0000-0001-7327-1619
                https://orcid.org/0000-0003-0983-4012
                https://orcid.org/0000-0001-8516-4618
                https://orcid.org/0000-0002-0387-3814
                https://orcid.org/0000-0001-9159-960X
                Article
                cells-09-01451
                10.3390/cells9061451
                7348822
                32545187
                446d3f7d-f120-490d-88ce-5a13da9d7492
                © 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
                : 20 May 2020
                : 08 June 2020
                Categories
                Review

                cancer,janus kinase,signal transducer and activator of transcription,natural compounds,targeted therapy

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