Unveiling the Power of Flavonoids: A Dynamic Exploration of Their Impact on Cancer Through Matrix Metalloproteinases Regulation

Overview

Journal Biomedicine (Taipei)

Specialty Biomedical Engineering

Date 2024 Jun 28

PMID 38939095

Authors

Peramaiyan Rajendran

Affiliations

Soon will be listed here.

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.

Citing Articles

Cellular and Molecular Mechanisms Modulated by Genistein in Cancer.

Naponelli V, Piscazzi A, Mangieri D Int J Mol Sci. 2025; 26(3).

PMID: 39940882 PMC: 11818640. DOI: 10.3390/ijms26031114.

Ugonin inhibits chondrosarcoma metastasis through suppressing cathepsin V via promoting miR-4799-5p expression.

Tran N, Chang T, Chi N, Lai K, Chen H, Fong Y Int J Biol Sci. 2025; 21(3):1144-1157.

PMID: 39897041 PMC: 11781170. DOI: 10.7150/ijbs.106827.

References

Zhang X, Chen C, Bhargava M, Torzilli P . A Comparative Study of Fibronectin Cleavage by MMP-1, -3, -13, and -14. Cartilage. 2015; 3(3):267-77. PMC: 4297120. DOI: 10.1177/1947603511435273. View

Fotsis T, Pepper M, Adlercreutz H, Fleischmann G, Hase T, Montesano R . Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci U S A. 1993; 90(7):2690-4. PMC: 46161. DOI: 10.1073/pnas.90.7.2690. View

Lian G, Wang Q, Mak T, Huang X, Yu X, Lan H . Inhibition of tumor invasion and metastasis by targeting TGF-β-Smad-MMP2 pathway with Asiatic acid and Naringenin. Mol Ther Oncolytics. 2021; 20:277-289. PMC: 7873580. DOI: 10.1016/j.omto.2021.01.006. View

Ju P, Ho Y, Chen P, Lee H, Lai S, Yang S . Kaempferol inhibits the cell migration of human hepatocellular carcinoma cells by suppressing MMP-9 and Akt signaling. Environ Toxicol. 2021; 36(10):1981-1989. DOI: 10.1002/tox.23316. View

Prado A, I M Batista R, Tanus-Santos J, Gerlach R . Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations. Biomolecules. 2021; 11(4). PMC: 8074048. DOI: 10.3390/biom11040585. View

Wang M, Ren D, Guo W, Huang S, Wang Z, Li Q . N-cadherin promotes epithelial-mesenchymal transition and cancer stem cell-like traits via ErbB signaling in prostate cancer cells. Int J Oncol. 2015; 48(2):595-606. DOI: 10.3892/ijo.2015.3270. View

Loffek S, Schilling O, Franzke C . Series "matrix metalloproteinases in lung health and disease": Biological role of matrix metalloproteinases: a critical balance. Eur Respir J. 2010; 38(1):191-208. DOI: 10.1183/09031936.00146510. View

Scheau C, Badarau I, Costache R, Caruntu C, Mihai G, Didilescu A . The Role of Matrix Metalloproteinases in the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma. Anal Cell Pathol (Amst). 2019; 2019:9423907. PMC: 6899323. DOI: 10.1155/2019/9423907. View

Grabowska M, Day M . Soluble E-cadherin: more than a symptom of disease. Front Biosci (Landmark Ed). 2011; 17(5):1948-64. PMC: 4183062. DOI: 10.2741/4031. View

10.

Chen R, Qi Q, Wang M, Li Q . Therapeutic potential of naringin: an overview. Pharm Biol. 2016; 54(12):3203-3210. DOI: 10.1080/13880209.2016.1216131. View

11.

Salem N, Kamal I, Al-Maghrabi J, Abuzenadah A, Peer-Zada A, Qari Y . High expression of matrix metalloproteinases: MMP-2 and MMP-9 predicts poor survival outcome in colorectal carcinoma. Future Oncol. 2016; 12(3):323-31. DOI: 10.2217/fon.15.325. View

12.

Kopustinskiene D, Jakstas V, Savickas A, Bernatoniene J . Flavonoids as Anticancer Agents. Nutrients. 2020; 12(2). PMC: 7071196. DOI: 10.3390/nu12020457. View

13.

Niland S, Riscanevo A, Eble J . Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression. Int J Mol Sci. 2022; 23(1). PMC: 8745566. DOI: 10.3390/ijms23010146. View

14.

Chen Y, Chang Y, Wang K, Chen P, Hseu Y, Chen K . Naringenin inhibited migration and invasion of glioblastoma cells through multiple mechanisms. Environ Toxicol. 2018; 34(3):233-239. DOI: 10.1002/tox.22677. View

15.

Alaseem A, Alhazzani K, Dondapati P, Alobid S, Bishayee A, Rathinavelu A . Matrix Metalloproteinases: A challenging paradigm of cancer management. Semin Cancer Biol. 2017; 56:100-115. DOI: 10.1016/j.semcancer.2017.11.008. View

16.

Jia X, Zhang Q, Xu L, Yao W, Wei L . Lotus leaf flavonoids induce apoptosis of human lung cancer A549 cells through the ROS/p38 MAPK pathway. Biol Res. 2021; 54(1):7. PMC: 7923640. DOI: 10.1186/s40659-021-00330-w. View

17.

Esparza J, Vilardell C, Calvo J, Juan M, Vives J, Urbano-Marquez A . Fibronectin upregulates gelatinase B (MMP-9) and induces coordinated expression of gelatinase A (MMP-2) and its activator MT1-MMP (MMP-14) by human T lymphocyte cell lines. A process repressed through RAS/MAP kinase signaling pathways. Blood. 1999; 94(8):2754-66. View

18.

Jian C, Ouyang H, Xiang X, Chen J, Li Y, Zhou X . Naringin protects myocardial cells from doxorubicin‑induced apoptosis partially by inhibiting the p38MAPK pathway. Mol Med Rep. 2017; 16(6):9457-9463. PMC: 5780003. DOI: 10.3892/mmr.2017.7823. View

19.

Cai R, Tressler C, Cheng M, Sonkar K, Tan Z, Paidi S . Primary breast tumor induced extracellular matrix remodeling in premetastatic lungs. Sci Rep. 2023; 13(1):18566. PMC: 10616170. DOI: 10.1038/s41598-023-45832-7. View

20.

Lee W, Chen W, Wang C, Lin W, Tseng T . Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and beta 4 integrin function in MDA-MB-231 breast cancer cells. Toxicol Appl Pharmacol. 2007; 226(2):178-91. DOI: 10.1016/j.taap.2007.09.013. View