Anti-Cancer Properties of Sesquiterpene Lactones

Sesquiterpene lactones are a diverse class of plant-derived terpenoids characterised by a 15-carbon backbone and an electrophilic α-methylene-γ-lactone motif. They are chiefly isolated from species of the Asteraceae family and have attracted substantial interest for their capacity to modulate multiple cancer-related pathways. Preclinical studies demonstrate that these compounds can inhibit pro-survival transcription factors such as NF-κB and STAT3, induce oxidative stress and mitochondrial dysfunction, provoke cell-cycle arrest, autophagy or apoptotic and necrotic cell death, and sensitize malignant cells to existing chemotherapeutics. Their activity against cancer stem-like cells and capacity to interfere with tumour-platelet interactions highlight both their mechanistic versatility and translational promise. Efforts to optimise pharmacokinetics and selectivity through semisynthetic derivatives have further advanced their potential as adjunctive or stand-alone anti-cancer agents.

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Anti-Cancer Properties of Sesquiterpene Lactones publication trend

The graph below shows the total number of articles in anti-cancer properties of sesquiterpene lactones across all publications each year (not limited to Nature Index journals).

Technical terms

Alpha-methylene-γ-lactone: Electrophilic functional group in sesquiterpene lactones that alkylates nucleophilic amino acids in protein targets.

Reactive oxygen species (ROS): Oxygen-derived radicals and peroxides that inflict oxidative damage, triggering cell death pathways in susceptible cancer cells.

Platelet-cancer interplay: Bidirectional interactions between platelets and tumour cells that facilitate metastasis, angiogenesis and tumour cell survival.

Autophagy: Intracellular degradation process that can promote survival under stress or contribute to programmed cell death, depending on context.

References

1. Discovery of 5‑Hydroxy-1,4-naphthoquinone (Juglone) Derivatives as Dual Effective Agents Targeting Platelet-Cancer Interplay through Protein Disulfide Isomerase Inhibition. Journal of Medicinal Chemistry (2024).
2. Applications of Sesquiterpene Lactones: A Review of Some Potential Success Cases. Applied Sciences (2020).
3. Sesquiterpenoids Lactones: Benefits to Plants and People. International Journal of Molecular Sciences (2013).
4. Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasis in a xenograft model of breast cancer. Cell Death & Disease (2013).
5. Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis. Cell Death & Disease (2016).