Bridging phytochemistry and oncology: flavonoids as next-generation anticancer therapeutics

To provide a comprehensive overview of the anticancer potential of flavonoids, with emphasis on their phytochemical sources, extraction approaches, structure-activity relationships, molecular mechanisms, nanotechnology-enabled delivery systems, and clinical applicability in cancer prevention and therapy.

The literature was reviewed to examine representative flavonoids, including quercetin, kaempferol, and epigallocatechin gallate, with particular focus on conventional and green extraction techniques, structural features associated with anticancer activity, modulation of cancer-related signalling pathways, and the development of flavonoid-loaded nanoparticles. Available clinical evidence regarding their efficacy, safety, and translational potential was also evaluated.

Flavonoids exhibit diverse biological activities, including antioxidant, anti-inflammatory, antiproliferative, pro-apoptotic, anti-angiogenic, and cell-cycle-regulatory effects. Their structural characteristics, particularly specific hydroxylation and substitution patterns, contribute to interactions with key molecular targets and oncogenic signalling pathways. Nanotechnology-based formulations have demonstrated potential for improving flavonoid solubility, bioavailability, stability, and tumour-targeted delivery. Although clinical studies indicate promising therapeutic and preventive effects, limitations related to bioavailability, formulation optimization, standardization, regulatory requirements, and insufficient clinical validation remain major barriers to translation.

Flavonoids represent promising phytochemical candidates for complementary and potentially integrative cancer therapeutics because of their multitargeted biological activities and favourable natural origin. However, their successful clinical translation requires standardized extraction and formulation protocols, improved delivery strategies, robust pharmacokinetic and clinical evaluation, and well-defined regulatory frameworks. Interdisciplinary collaboration between phytochemistry, nanotechnology, pharmacology, and oncology will be essential for establishing flavonoids as reliable anticancer agents.