Phytochemical Therapeutics in Cancer and Inflammatory Disorders

Phytochemical therapeutics harness biologically active compounds derived from plants to prevent or treat malignancies and inflammatory conditions. Major classes include polyphenols, alkaloids, terpenoids and acetogenins, each capable of modulating multiple molecular targets. These natural products may inhibit aberrant cell proliferation, induce programmed cell death and attenuate chronic inflammation via regulation of signalling cascades such as PI3K/AKT, NF-κB and JAK/STAT. Advances in formulation science—particularly nanoparticle and liposomal delivery—have improved solubility, bioavailability and tumour specificity, reducing systemic toxicity. Beyond oncology, selected phytochemicals display potent anti-inflammatory and immunomodulatory activities, offering promise for diseases in which inflammation underlies tissue damage. Continual elucidation of mechanisms, coupled with translational studies, underscores the global significance of plant-derived agents as complementary or alternative interventions in cancer therapy and the management of inflammatory disorders.

Research from Nature Portfolio

Recent studies have elucidated the anticancer potential of selected flavonoids through detailed mechanistic investigation. One report isolated flavonoids from a medicinal plant and demonstrated their capacity to bind the ATP-binding pocket of PI3Kγ, leading to downregulation of the PI3K/AKT/mTOR/p70S6K/ULK signalling axis. This intervention induced G2/M cell-cycle arrest, apoptosis and autophagy in breast cancer cells, establishing a novel route by which dietary polyphenols exert antiproliferative effects. In another foundational study, ailanthone—a quassinoid from the bark of Ailanthus altissima—was shown to provoke G0/G1 arrest and trigger DNA-damage responses via activation of the ATM/ATR pathway in hepatocellular carcinoma models. Its mitochondrion-mediated apoptosis involved modulation of PI3K/AKT signalling and was validated in tumour xenografts with minimal adverse effects, highlighting its translational promise.

Phytochemical Therapeutics in Cancer and Inflammatory Disorders publication trend

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

Technical terms

Phytochemicals: Bioactive compounds produced by plants that modulate cellular processes and may confer therapeutic benefits.

Acetogenins: Polyketide-derived secondary metabolites found mainly in Annonaceae, known for potent cytotoxic and antitumour activities.

Flavonoids: Polyphenolic molecules ubiquitous in fruits and vegetables that regulate signalling pathways involved in cell proliferation, apoptosis and autophagy.

Liposomal co-delivery: A formulation approach using lipid vesicles to encapsulate two or more agents, improving solubility, stability and targeted delivery to diseased tissue.

PI3K/AKT/mTOR pathway: A central intracellular signalling network governing cell growth, survival and metabolism; frequently dysregulated in cancer.

Apoptosis: Programmed cell death characterised by caspase activation, DNA fragmentation and membrane blebbing.

Autophagy: A regulated process of lysosomal degradation that recycles cellular components and can lead to cell death under stress conditions.

References

1. Enhanced anti-glioma activity of annonaceous acetogenins based on a novel liposomal co-delivery system with ginsenoside Rh2. Drug Delivery (2024).
2. Comparative phytochemical and pharmacological analysis of two cultivars of Annona squamosa L. cultivated in Egypt. npj Science of Food (2025).
3. Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells. Scientific Reports (2018).
4. Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo. Scientific Reports (2015).