Steroidal Saponins in Cancer Therapeutics

Steroidal saponins are a class of naturally occurring glycosides characterised by a steroidal aglycone linked to one or more sugar moieties. These compounds, abundant in various medicinal plants such as Paris polyphylla, have attracted growing interest in oncology due to their capacity to modulate multiple hallmarks of cancer. Mechanistic studies have revealed that steroidal saponins can induce programmed cell death, inhibit cell proliferation, suppress metastasis and overcome chemoresistance. Among the most studied molecules are polyphyllins and dioscin-derived analogues, which exert antitumour effects via activation of intrinsic and extrinsic apoptotic pathways, generation of reactive oxygen species and regulation of autophagic processes. In addition, several steroidal saponins interfere with key signalling cascades, including the Wnt/β-catenin and AKT/mTOR pathways, thereby halting tumour growth and sensitising cells to conventional chemotherapy. Preclinical models have further highlighted their immunomodulatory potential and favourable safety profiles. Taken together, current research underscores the global significance of steroidal saponins as multitargeted agents and paves the way for their integration into novel therapeutic regimens.

Research from Nature Portfolio

Recent studies have elucidated the biosynthetic origins and therapeutic actions of steroidal saponins. A foundational analysis of spiroketal steroid biosynthesis has uncovered the independent recruitment of cytochrome P450 enzymes in distinct plant lineages to produce diosgenin, a precursor for clinical steroid drugs. This work provides a blueprint for sustainable engineering of diosgenin analogues in heterologous hosts, facilitating large-scale production of anticancer saponins. In parallel, investigations into polyphyllin I have demonstrated potent activity against osteosarcoma in orthotopic mouse models. Treatment with this saponin analogue resulted in G2/M cell-cycle arrest, apoptosis induction and inhibition of invasion, effects that were traced to inactivation of the Wnt/β-catenin signalling axis. These discoveries highlight both the natural biosynthetic diversity and targeted mechanistic efficacy of steroidal saponins in cancer therapy.

Steroidal Saponins in Cancer Therapeutics publication trend

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

Technical terms

Steroidal saponins: Natural glycosides with a steroid nucleus and sugar chains, noted for cytotoxic and immunomodulatory properties.

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

Autophagy: Cellular degradation process involving lysosomal breakdown of cytoplasmic components, which can contribute to cell survival or death.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can damage cellular components or signal for cell death.

Wnt/β-catenin pathway: A signalling cascade that regulates gene transcription and cell proliferation, often dysregulated in cancer.

AKT/mTOR signalling pathway: A central kinase cascade controlling cell growth, metabolism and survival, commonly hyperactivated in tumours.

Cytochrome P450: A family of haem-containing enzymes that catalyse oxidation reactions in the biosynthesis of steroids and other metabolites.

References

1. The genus Paris: a fascinating resource for medicinal and botanical studies. Horticulture Research (2024).
2. Repeated evolution of cytochrome P450-mediated spiroketal steroid biosynthesis in plants. Nature Communications (2019).
3. Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo. Scientific Reports (2017).
4. Polyphyllin I induces autophagy and cell cycle arrest via inhibiting PDK1/Akt/mTOR signal and downregulating cyclin B1 in human gastric carcinoma HGC-27 cells. Biomedicine & Pharmacotherapy (2019).
5. Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS‐Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide. Oxidative Medicine and Cellular Longevity (2019).