Exploring Flavonoids as Regulators of MMP-2 and MMP-9 in Cancer Pathogenesis

Last few decades, extensive research efforts have been dedicated to uncovering novel cancer treatments. Among the most vital targets in this pursuit are matrix metalloproteinases (MMPs), enzymes integral to the progression and spread of cancer. Their role in tumor development and metastasis positions MMPs as key players in cancer pathogenesis, offering promising avenues for therapeutic intervention. Specifically, MMP-2 and MMP-9 have emerged as promising targets in cancer treatment based on their critical roles in cell invasion, angiogenesis, immune evasion, and metastasis. Studies indicate the potential of plant-derived natural products as anticancer agents through the regulation of MMP activity. Among various phytochemicals, flavonoids are reported to exhibit inhibitory activities against MMPs and antioxidant properties that present them as candidates for anticancer molecules. In this study, the potential of flavonoids as anticancer agents was explored by investigating the effects of flavonoids on (i) cancer cell viability and migration, (ii) enzymatic activity and cellular expression of MMP-2/9, and (iii) the MAPK signaling pathway. Docking simulation data regarding the interactions between MMP-2/9 and selected flavonoids provide an in-depth look at the potential mechanisms through which these molecules suppress the enzymatic activities of MMPs. Select flavonoids exhibited notable efficacy in suppressing cell proliferation and migration in A549 cells, which may be a consequence of their ability to attenuate MMP activity and expression through the suppression of the MAPK signaling pathway. These observations demonstrate the prospect of flavonoids as a naturally occurring molecular framework for the development of novel anticancer therapeutics.