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      Rediscovery of Traditional Plant Medicine: An Underestimated Anticancer Drug of Chelerythrine

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          Abstract

          In many studies, the extensive and significant anticancer activity of chelerythrine (CHE) was identified, which is the primary natural active compound in four traditional botanical drugs and can be applied as a promising treatment in various solid tumors. So this review aimed to summarize the anticancer capacities and the antitumor mechanism of CHE. The literature searches revolving around CHE have been carried out on PubMed, Web of Science, ScienceDirect, and MEDLINE databases. Increasing evidence indicates that CHE, as a benzophenanthridine alkaloid, exhibits its excellent anticancer activity as CHE can intervene in tumor progression and inhibit tumor growth in multiple ways, such as induction of cancer cell apoptosis, cell cycle arrest, prevention of tumor invasion and metastasis, autophagy-mediated cell death, bind selectively to telomeric G-quadruplex and strongly inhibit the telomerase activity through G-quadruplex stabilization, reactive oxygen species (ROS), mitogen-activated protein kinase (MAPK), and PKC. The role of CHE against diverse types of cancers has been investigated in many studies and has been identified as the main antitumor drug candidate in drug discovery programs. The current complex data suggest the potential value in clinical application and the future direction of CHE as a therapeutic drug in cancer. Furthermore, the limitations and the present problems are also highlighted in this review. Despite the unclearly delineated molecular targets of CHE, extensive research in this area provided continuously fresh data exploitable in the clinic while addressing the present requirement for further studies such as toxicological studies, combination medication, and the development of novel chemical methods or biomaterials to extend the effects of CHE or the development of its derivatives and analogs, contributing to the effective transformation of this underestimated anticancer drug into clinical practice. We believe that this review can provide support for the clinical application of a new anticancer drug in the future.

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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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            Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods

            Estimates of the worldwide incidence and mortality from 36 cancers and for all cancers combined for the year 2018 are now available in the GLOBOCAN 2018 database, compiled and disseminated by the International Agency for Research on Cancer (IARC). This paper reviews the sources and methods used in compiling the cancer statistics in 185 countries. The validity of the national estimates depends upon the representativeness of the source information, and to take into account possible sources of bias, uncertainty intervals are now provided for the estimated sex- and site-specific all-ages number of new cancer cases and cancer deaths. We briefly describe the key results globally and by world region. There were an estimated 18.1 million (95% UI: 17.5-18.7 million) new cases of cancer (17 million excluding non-melanoma skin cancer) and 9.6 million (95% UI: 9.3-9.8 million) deaths from cancer (9.5 million excluding non-melanoma skin cancer) worldwide in 2018.
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              Tumor metastasis: molecular insights and evolving paradigms.

              Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to generate macroscopic metastases. Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting. Copyright © 2011 Elsevier Inc. All rights reserved.
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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
                01 June 2022
                2022
                : 13
                : 906301
                Affiliations
                [1] 1 Department of Oncology , Hospital of Chengdu University of Traditional Chinese Medicine , Chengdu, China
                [2] 2 Hospital of Chengdu University of Traditional Chinese Medicine , Chengdu, China
                [3] 3 State Key Laboratory of Southwestern Chinese Medicine Resources , School of Pharmacy , Chengdu University of Traditional Chinese Medicine , Chengdu, China
                [4] 4 Hospital of Chengdu University of Traditional Chinese Medicine , School of Clinical Medicine , Chengdu University of Traditional Chinese Medicine , Chengdu, China
                [5] 5 Department of Gastroenterology , Hospital of Chengdu University of Traditional Chinese Medicine , Chengdu, China
                [6] 6 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province , Hospital of Chengdu University of Traditional Chinese Medicine , Chengdu, China
                [7] 7 Geriatric Department , Hospital of Chengdu University of Traditional Chinese Medicine , Chengdu, China
                Author notes

                Edited by: Shuai Ji, Xuzhou Medical University, China

                Reviewed by: Tanaya Roychowdhury, Indian Institute of Chemical Biology (CSIR), India

                Rudradip Pattanayak, University of Alabama at Birmingham, United States

                Lina Wen, Capital Medical University, China

                *Correspondence: Jinhao Zeng, zengjinhao@ 123456cdutcm.edu.cn ; Jianyuan Tang, tangjy@ 123456cdutcm.edu.cn
                [ † ]

                These authors have contributed equally to this work

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

                Article
                906301
                10.3389/fphar.2022.906301
                9198297
                35721116
                a8de86ff-f206-4156-8414-097f2606bb0c
                Copyright © 2022 Chen, Qi, Ma, Xiao, Liu, Xia, Xiang, Zeng and Tang.

                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
                : 28 March 2022
                : 26 April 2022
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                chelerythrine,traditional botanical drugs,anticancer,molecular mechanism,future direction

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