Flavonoids as regulators of TIMPs expression in cancer: Consequences, opportunities, and challenges

Cancer is one of the leading causes of death in patients worldwide, where invasion and metastasis are directly responsible for this statement. Although cancer therapy has progressed in recent years, current therapeutic approaches are ineffective due to toxicity and chemoresistance. Therefore, it is essential to evaluate other treatment options, and natural products are a promising alternative as they show antitumor properties in different study models. This review describes the regulation of tissue inhibitors of metalloproteinases (TIMPs) expression and the role of flavonoids as molecules with the antitumor activity that targets TIMPs therapeutically. These inhibitors regulate tissue extracellular matrix (ECM) turnover; they inhibit matrix metalloproteinases (MMPs), cell migration, invasion, and angiogenesis and induce apoptosis in tumor cells. Data obtained in cell lines and in vivo models suggest that flavonoids are chemopreventive and cytotoxic against various types of cancer through several mechanisms. Flavonoids also regulate crucial signaling pathways such as focal adhesion kinase (FAK), phosphatidylinositol-3-kinase (PI3K)-Akt, signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF kappa B), and mitogen-activated protein kinase (MAPK) involved in cancer cell migration, invasion, and metastasis. All these data reposition flavonoids as excellent candidates for use in cancer therapy.

Automated summary

Cancer is a leading cause of death globally, with invasion and metastasis being directly responsible. Current therapeutic approaches for cancer suffer from toxicity and chemoresistance, highlighting the need for alternative treatment options. Natural products, particularly flavonoids, have shown promise as they possess antitumor properties in various study models. This review discusses the regulation of tissue inhibitors of metalloproteinases (TIMPs) expression and the role of flavonoids as therapeutic molecules that target TIMPs. Flavonoids exhibit chemopreventive and cytotoxic effects against different types of cancer through various mechanisms and also regulate crucial signaling pathways involved in cancer cell migration, invasion, and metastasis.