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      To explore the effect of kaempferol on non-small cell lung cancer based on network pharmacology and molecular docking

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          Abstract

          Non-small cell lung cancer (NSCLC) is a common pathological type of lung cancer, which has a serious impact on human life, health, psychology and life. At present, chemotherapy, targeted therapy and other methods commonly used in clinic are prone to drug resistance and toxic side effects. Natural extracts of traditional Chinese medicine (TCM) have attracted wide attention in cancer treatment because of their small toxic and side effects. Kaempferol is a flavonoid from natural plants, which has been proved to have anticancer properties in many cancers such as lung cancer, but the exact molecular mechanism is still unclear. Therefore, on the basis of in vitro experiments, we used network pharmacology and molecular docking methods to study the potential mechanism of kaempferol in the treatment of non-small cell lung cancer. The target of kaempferol was obtained from the public database (PharmMapper, Swiss target prediction), and the target of non-small cell lung cancer was obtained from the disease database (Genecards and TTD). At the same time, we collected gene chips GSE32863 and GSE75037 in conjunction with GEO database to obtain differential genes. By drawing Venn diagram, we get the intersection target of kaempferol and NSCLC. Through enrichment analysis, PI3K/AKT is identified as the possible key signal pathway. PIK3R1, AKT1, EGFR and IGF1R were selected as key targets by topological analysis and molecular docking, and the four key genes were further verified by analyzing the gene and protein expression of key targets. These findings provide a direction for further research of kaempferol in the treatment of NSCLC.

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          Most cited references36

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention.

            Kaempferol is a polyphenol antioxidant found in fruits and vegetables. Many studies have described the beneficial effects of dietary kaempferol in reducing the risk of chronic diseases, especially cancer. Epidemiological studies have shown an inverse relationship between kaempferol intake and cancer. Kaempferol may help by augmenting the body's antioxidant defence against free radicals, which promote the development of cancer. At the molecular level, kaempferol has been reported to modulate a number of key elements in cellular signal transduction pathways linked to apoptosis, angiogenesis, inflammation, and metastasis. Significantly, kaempferol inhibits cancer cell growth and angiogenesis and induces cancer cell apoptosis, but on the other hand, kaempferol appears to preserve normal cell viability, in some cases exerting a protective effect. The aim of this review is to synthesize information concerning the extraction of kaempferol, as well as to provide insights into the molecular basis of its potential chemo-preventative activities, with an emphasis on its ability to control intracellular signaling cascades that regulate the aforementioned processes. Chemoprevention using nanotechnology to improve the bioavailability of kaempferol is also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Kaempferol: A Key Emphasis to Its Anticancer Potential

              A marked decrease in human cancers, including breast cancer, bone cancer, and cervical cancer, has been linked to the consumption of vegetable and fruit, and the corresponding chemoprotective effect has been associated with the presence of several active molecules, such as kaempferol. Kaempferol is a major flavonoid aglycone found in many natural products, such as beans, bee pollen, broccoli, cabbage, capers, cauliflower, chia seeds, chives, cumin, moringa leaves, endive, fennel, and garlic. Kaempferol displays several pharmacological properties, among them antimicrobial, anti-inflammatory, antioxidant, antitumor, cardioprotective, neuroprotective, and antidiabetic activities, and is being applied in cancer chemotherapy. Specifically, kaempferol-rich food has been linked to a decrease in the risk of developing some types of cancers, including skin, liver, and colon. The mechanisms of action include apoptosis, cell cycle arrest at the G2/M phase, downregulation of epithelial-mesenchymal transition (EMT)-related markers, and phosphoinositide 3-kinase/protein kinase B signaling pathways. In this sense, this article reviews data from experimental studies that investigated the links between kaempferol and kaempferol-rich food intake and cancer prevention. Even though growing evidence supports the use of kaempferol for cancer prevention, further preclinical and clinical investigations using kaempferol or kaempferol-rich foods are of pivotal importance before any public health recommendation or formulation using kaempferol.
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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
                18 July 2023
                2023
                : 14
                : 1148171
                Affiliations
                [1] 1 Innovative Institute of Chinese Medicine and Pharmacy , Shandong University of Traditional Chinese Medicine , Jinan, China
                [2] 2 Experimental Center , Shandong University of Traditional Chinese Medicine , Jinan, China
                [3] 3 Department of Scientific Research , Shandong University of Traditional Chinese Medicine , Jinan, China
                [4] 4 Shandong Tai’an Central Hospital , Tai’an, China
                [5] 5 Key Laboratory of Traditional Chinese Medicine Classical Theory , Ministry of Education , Shandong University of Traditional Chinese Medicine , Jinan, China
                [6] 6 Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research , Shandong University of Traditional Chinese Medicine , Jinan, China
                [7] 7 Daiyue District Maternal and Child Health Hospital , Tai’an, Shandong, China
                [8] 8 School of Pharmacy , Shandong University of Traditional Chinese Medicine , Jinan, China
                Author notes

                Edited by: Carmela Spagnuolo, National Research Council (CNR), Italy

                Reviewed by: Idolo Tedesco, National Research Council (CNR), Italy

                Wisnu Ananta Kusuma, IPB University, Indonesia

                *Correspondence: Qingjun Zhu, zhuqingjuncn@ 123456hotmail.com ; Peng Sun, sunpeng@ 123456sdutcm.edu.cn
                Article
                1148171
                10.3389/fphar.2023.1148171
                10392700
                5adee701-c3d8-4b18-ac0b-144619ed38ef
                Copyright © 2023 Zhang, Liu, Zhang, Wu, Liu, Liu, Wang, Miao, Deng, Cao, Shang, Zhu and Sun.

                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
                : 19 January 2023
                : 27 April 2023
                Funding
                This work was supported by the National Natural Science Foundation of China (82170085, 81970064, 81870001, 81670064, and 31670365), the Natural Science Foundation of Shandong Province (ZR2020MH009 and ZR2020MH010), the National Natural Science Foundation of China (NSFC, Nos. 81874419, 81673719, and 81303074), National Health Commission of the People’s Republic of China (Nos 2017ZX09301064 and 2017ZX09301064002), Natural Science Foundation of Shandong Province (Nos ZR2020MB108 and ZR2019MH063), Central Government Guided Local Science and Technology Development Project (22-1-3-11-zyyd-nsh-3), Shandong Major Innovation Project (2022CXGC020514) and the Youth Research and Innovation Team of TCM-Based Neuroimmune Pharmacology, University of Shandong Traditional Chinese Medicine (No. 22202112).
                Categories
                Pharmacology
                Original Research
                Custom metadata
                Pharmacology of Anti-Cancer Drugs

                Pharmacology & Pharmaceutical medicine
                kaempferol (compound cid 5280863),network pharmacology,nsclc,molecular docking, in vitro experiments

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