Molecular Mechanisms of Action of Polyphenols Against Cancer: Experimental and in silico Evaluations

Abstract

Flavonoids, a diverse collection of phytonutrients in leaves, stems, roots, fruits, and vegetables, are classified into various sub-classes, including flavanols. These substances are widespread in a variety of traditional medicinal plants, where they display unique chemical compositions and significant bioactivity. Flavanols, distinguished by their hydroxyl groups, have attracted considerable interest for their possible anti-cancer properties. This chapter offers a comprehensive summary of flavanols, highlighting their role in preventing and treating cancer. Flavanols have demonstrated potential in regulating oxidative stress and serving as potent antioxidants, which can shield cells from DNA damage and mutations induced by oxidative stress. Moreover, flavanols can trigger programmed cell death in cancer cells occurs through various mechanisms, such as activating caspases and inhibiting anti-cell death proteins. Transporters influenced by flavanols in multiple drug-resistant cancer cells, cell lines and animal models further illustrate their potential, suggesting that flavanols can overcome some forms of drug resistance in cancer treatment. Future research should concentrate on clinically exploring flavanols and integrating them into comprehensive cancer care strategies. This chapter underscores the considerable potential of flavanols as natural anti-cancer agents and advocates for their inclusion in future cancer research and treatment approaches. © 2025 The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG.