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      Unveiling the power of flavonoids: A dynamic exploration of their impact on cancer through matrix metalloproteinases regulation

      review-article
      Author(s): a , b ,
      Publication date (Electronic, collection):
      Publication date (Electronic, pub):
      Journal: BioMedicine
      Publisher: China Medical University
      Keywords: MMP, Metastasis, Flavonoids, Apigenin, Naringin, Kaempferol, Malvidin, Genistein

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          Abstract

          Cancer stands as a significant contributor to global mortality rates, primarily driven by its progression and widespread dissemination. Despite notable strides in cancer therapy, the efficacy of current treatment strategies is compromised due to their inherent toxicity and the emergence of chemoresistance. Consequently, there is a critical need to evaluate alternative therapeutic approaches, with natural compounds emerging as promising candidates, showcasing demonstrated anticancer capabilities in various research models. This review manuscript presents a comprehensive examination of the regulatory mechanisms governing the expression of matrix metalloproteinases (MMPs) and delves into the potential therapeutic role of flavonoids as agents exhibiting specific anticancer activity against MMPs. The primary aim of this study is to elucidate the diverse functions associated with MMP production in cancer and to investigate the potential of flavonoids in modulating MMP expression to inhibit metastasis.

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          Flavonoids: an overview

          A. N. Panche, A. D. Diwan, S. Chandra (2016)
          Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.
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            Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting.

            Chrisostomi Gialeli, Achilleas Theocharis, Nikos K Karamanos (2011)
            Matrix metalloproteinases (MMPs) consist of a multigene family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases implicated in pathological processes, such as carcinogenesis. In this regard, their activity plays a pivotal role in tumor growth and the multistep processes of invasion and metastasis, including proteolytic degradation of ECM, alteration of the cell-cell and cell-ECM interactions, migration and angiogenesis. The underlying premise of the current minireview is that MMPs are able to proteolytically process substrates in the extracellular milieu and, in so doing, promote tumor progression. However, certain members of the MMP family exert contradicting roles at different stages during cancer progression, depending among other factors on the tumor stage, tumor site, enzyme localization and substrate profile. MMPs are therefore amenable to therapeutic intervention by synthetic and natural inhibitors, providing perspectives for future studies. Multiple therapeutic agents, called matrix metalloproteinase inhibitors (MMPIs) have been developed to target MMPs, attempting to control their enzymatic activity. Even though clinical trials with these compounds do not show the expected results in most cases, the field of MMPIs is ongoing. This minireview critically evaluates the role of MMPs in relation to cancer progression, and highlights the challenges, as well as future prospects, for the design, development and efficacy of MMPIs. © 2010 The Authors Journal compilation © 2010 FEBS.
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              The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges

              Chin-Yap Loh, Jian Yi Chai, Ting Fang Tang … (2019)
              Epithelial-to-Mesenchymal Transition (EMT) has been shown to be crucial in tumorigenesis where the EMT program enhances metastasis, chemoresistance and tumor stemness. Due to its emerging role as a pivotal driver of tumorigenesis, targeting EMT is of great therapeutic interest in counteracting metastasis and chemoresistance in cancer patients. The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin, and this process is regulated by a complex network of signaling pathways and transcription factors. In this review, we summarized the recent understanding of the roles of E- and N-cadherins in cancer invasion and metastasis as well as the crosstalk with other signaling pathways involved in EMT. We also highlighted a few natural compounds with potential anti-EMT property and outlined the future directions in the development of novel intervention in human cancer treatments. We have reviewed 287 published papers related to this topic and identified some of the challenges faced in translating the discovery work from bench to bedside.
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                Author and article information

                Contributors
                Peramaiyan Rajendran: Role: ConceptualizationRole: Formal analysisRole: Writing - original draft
                Journal
                Journal ID (nlm-ta): Biomedicine (Taipei)
                Journal ID (iso-abbrev): Biomedicine (Taipei)
                Title: BioMedicine
                Publisher: China Medical University
                ISSN (Print): 2211-8020
                ISSN (Electronic): 2211-8039
                Publication date (Electronic, collection): 2024
                Publication date (Electronic, pub): 01 June 2024
                Volume: 14
                Issue: 2
                Pages: 12-28
                Affiliations
                [a ]Department of Biological Sciences, College of Science, King Faisal University, Al Ahsa, 31982, Saudi Arabia
                [b ]Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600 077, Tamil Nadu, India
                Author notes
                Article
                Publisher ID: bmed-14-02-012
                DOI: 10.37796/2211-8039.1447
                PMC ID: 11204124
                PubMed ID: 38939095
                SO-VID: 196269b4-6b98-45b3-b59a-b682070b1404
                Copyright © © the Author(s)
                License:

                This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 29 September 2023
                Date revision received : 15 November 2023
                Date accepted : 22 December 2023
                Funding
                Funded by: Deanship of Scientific Research, Vice Presidency for Graduate studies and Scientific Research, King Faisal University Saudi Arabia
                Award ID: 5036
                This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate studies and Scientific Research, King Faisal University Saudi Arabia [Grant 5036]
                Categories
                Subject: Review Article

                Keywords: mmp,metastasis,flavonoids,apigenin,naringin,kaempferol,malvidin,genistein
                Data availability:
                Keywords: mmp, metastasis, flavonoids, apigenin, naringin, kaempferol, malvidin, genistein

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