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      Apigenin inhibits epithelial-mesenchymal transition of human colon cancer cells through NF-κB/Snail signaling pathway

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          Abstract

          Colon cancer is a leading cause of cancer-related deaths worldwide. The epithelial-mesenchymal transition (EMT) plays an important role in tumor metastasis of colon cancer. We first evaluated the effects of EMT-related transcription factors on the prognosis of colon cancer through analysis the data obtained from The Cancer Genome Atlas (TCGA). And then we screened a series of Chinese medicine monomers to find effect EMT inhibitors. First, Snail is a more important EMT transcription factors for colon cancer prognosis, compared with Twist and Slug. Then, we found that apigenin effectively inhibits the activity of Snail. Apigenin could inhibit the EMT, migration, and invasion of human colon cancer cells in vitro and in vivo through the NF-κB/Snail pathway. Snail is a key regulator of EMT in colon cancer and Snail inhibitor apigenin may be a therapeutic application for patients with colon cancer.

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          TNF-α/NF-κB/Snail pathway in cancer cell migration and invasion

          Y. Wu, B P Zhou (2010)
          Tumour necrosis factor-alpha (TNF-α) is an important inflammatory factor that acts as a master switch in establishing an intricate link between inflammation and cancer. A wide variety of evidence has pointed to a critical role of TNF-α in tumour proliferation, migration, invasion and angiogenesis. The function of TNF-α as a key regulator of the tumour microenvironment is well recognised. We will emphasise the contribution of TNF-α and the nuclear factor-κB pathway on tumour cell invasion and metastasis. Understanding the mechanisms underlying inflammation-mediated metastasis will reveal new therapeutic targets for cancer prevention and treatment.
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            Apigenin: a promising molecule for cancer prevention.

            Sanjeev Shukla, Sanjay Gupta (2010)
            Apigenin, a naturally occurring plant flavone, abundantly present in common fruits and vegetables, is recognized as a bioactive flavonoid shown to possess anti-inflammatory, antioxidant and anticancer properties. Epidemiologic studies suggest that a diet rich in flavones is related to a decreased risk of certain cancers, particularly cancers of the breast, digestive tract, skin, prostate and certain hematological malignancies. It has been suggested that apigenin may be protective in other diseases that are affected by oxidative process, such as cardiovascular and neurological disorders, although more research needs to be conducted in this regard. Human clinical trials examining the effect of supplementation of apigenin on disease prevention have not been conducted, although there is considerable potential for apigenin to be developed as a cancer chemopreventive agent.
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              Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition.

              S Julien, I. Puig, E Caretti … (2007)
              Carcinoma progression is associated with the loss of epithelial features, and the acquisition of mesenchymal characteristics and invasive properties by tumour cells. The loss of cell-cell contacts may be the first step of the epithelium mesenchyme transition (EMT) and involves the functional inactivation of the cell-cell adhesion molecule E-cadherin. Repression of E-cadherin expression by the transcription factor Snail is a central event during the loss of epithelial phenotype. Akt kinase activation is frequent in human carcinomas, and Akt regulates various cellular mechanisms including EMT. Here, we show that Snail activation and consequent repression of E-cadherin may depend on AKT-mediated nuclear factor-kappaB (NF-kappaB) activation, and that NF-kappaB induces Snail expression. Expression of the NF-kappaB subunit p65 is sufficient for EMT induction, validating this signalling module during EMT. NF-kappaB pathway activation is associated with tumour progression and metastasis of several human tumour types; E-cadherin acts as a metastasis suppressor protein. Thus, this signalling and transcriptional network linking AKT, NF-kappaB, Snail and E-cadherin during EMT is a potential target for antimetastatic therapeutics.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biosci Rep
                Journal ID (iso-abbrev): Biosci. Rep
                Journal ID (hwp): ppbioscirep
                Journal ID (publisher-id): BSR
                Title: Bioscience Reports
                Publisher: Portland Press Ltd.
                ISSN (Print): 0144-8463
                ISSN (Electronic): 1573-4935
                Publication date (Electronic preprint): 09 April 2019
                Publication date Collection: 31 May 2019
                Publication date (Electronic): 14 May 2019
                Volume: 39
                Issue: 5
                Electronic Location Identifier: BSR20190452
                Affiliations
                [1 ]Department of Traditional Chinese Medicine, Huadong Hospital, Shanghai 200040, China
                [2 ]Department of Gastrology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
                [3 ]Department of Oncology, Jing’an District Central Hospital of Shanghai (Huashan Hospital, Fudan University, Jing’an branch200040), China
                Author notes
                Correspondence: Li Han ( xuzhangmail123@ 123456163.com )
                [*]

                These authors contribute equally to this work

                Author information
                http://orcid.org/0000-0002-6842-7620
                Article
                DOI: 10.1042/BSR20190452
                PMC ID: 6522743
                PubMed ID: 30967496
                SO-VID: b02f238a-bcd2-4cb6-9463-6767e0942d0f
                Copyright © © 2019 The Author(s).
                License:

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                Date received : 28 February 2019
                Date revision received : 02 April 2019
                Date accepted : 02 April 2019
                Page count
                Pages: 11
                Categories
                Subject: Research Articles
                Subject: Research Article
                Subject: 53
                Subject: 21
                Subject: 39

                ScienceOpen disciplines: Life sciences
                Keywords: apigenin,colon cancer cells,epithelial-mesenchymal transition (emt),snail
                Data availability:
                ScienceOpen disciplines: Life sciences
                Keywords: apigenin, colon cancer cells, epithelial-mesenchymal transition (emt), snail

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