Flavonoid Bioactivity in Cancer Therapeutics

Flavonoids are naturally occurring polyphenols classified into six major subclasses—flavonols, flavones, flavanones, flavanols, isoflavonoids and anthocyanidins—ubiquitous in fruits, vegetables, teas and wines. Interest in their oncological potential arises from a dual capacity to scavenge excessive reactive oxygen species in healthy tissues while generating pro-oxidant stress in malignant cells. These compounds modulate key signalling networks such as PI3K/Akt/mTOR, Wnt/β-catenin and MAPK/ERK to induce apoptosis, autophagy and cell-cycle arrest, and to inhibit angiogenesis, invasion and metastatic spread. Their relatively low toxicity, combined with chemosensitising properties and the ability to remodel the tumour microenvironment, positions flavonoids as attractive adjuncts to conventional therapies. Challenges remain in translation, notably variable bioavailability, rapid metabolism and limited tissue delivery, which have stimulated the development of novel formulation strategies including nano-encapsulation and conjugation to improve pharmacokinetics and therapeutic indices.

Research from Nature Portfolio

Recent foundational work has demonstrated that quercetin directly intercalates with DNA in tumour cells, triggering S-phase cell-cycle arrest and activating the intrinsic mitochondrial pathway of apoptosis. In murine models bearing solid tumours, quercetin administration at doses significantly lower than comparable flavonoids led to marked tumour regression and a substantial increase in survival time. Importantly, quercetin exhibited selective cytotoxicity, sparing normal cells and reducing stromal-cell-driven chemoresistance, thereby underscoring its promise as both a monotherapy and a sensitiser in combination regimens.

Flavonoid Bioactivity in Cancer Therapeutics publication trend

The graph below shows the total number of articles in flavonoid bioactivity in cancer therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can damage cellular components and influence signalling pathways.

Apoptosis: Programmed cell death characterised by ordered cellular dismantling and minimal inflammation.

Autophagy: Intracellular degradation process that recycles damaged organelles and proteins under stress conditions.

Cell-cycle arrest: The halting of cell division at a specific checkpoint, preventing proliferation of damaged cells.

PI3K/Akt/mTOR pathway: A central signalling cascade regulating cell growth, survival and metabolism, often dysregulated in cancers.

Bioavailability: The proportion of an administered compound that reaches systemic circulation and is available for therapeutic action.

References

1. Flavonoids as Anticancer Agents. Nutrients (2020).
2. Flavonoid Bioavailability and Attempts for Bioavailability Enhancement. Nutrients (2013).
3. Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis. Scientific Reports (2016).
4. The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism. International Journal of Molecular Sciences (2019).