Therapeutic Applications of Sesquiterpenes in Cancer Biology

Sesquiterpenes, a major class of plant-derived terpenoids, have emerged as promising agents in cancer research through multifaceted mechanisms that include induction of programmed cell death, inhibition of tumour proliferation and migration, modulation of key signalling cascades and enhancement of conventional chemotherapeutic efficacy. Compounds such as β-caryophyllene and its oxide derivative have been shown to engage the endocannabinoid system, selectively activating cannabinoid receptor type 2 to trigger apoptosis in malignant cells without provoking psychoactive effects. Beyond receptor-mediated processes, sesquiterpenes interfere with the mitogen-activated protein kinase and PI3K/AKT/mTOR pathways, downregulate anti-apoptotic proteins and suppress inflammatory mediators that foster tumour growth. Importantly, their low toxicity profile in normal tissues and capacity to sensitize resistant cancer cells to agents such as doxorubicin and cisplatin position sesquiterpenes as attractive adjuvants. Advances in formulation—ranging from nano-encapsulation to combination therapies—have further expanded their clinical potential, offering routes to improved bioavailability and targeted delivery. As interest intensifies in natural product oncology, sesquiterpenes stand out for their dual anticancer and analgesic properties, supporting a holistic approach to cancer management that can attenuate tumour progression and alleviate treatment-associated pain.

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Therapeutic Applications of Sesquiterpenes in Cancer Biology publication trend

The graph below shows the total number of articles in therapeutic applications of sesquiterpenes in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Sesquiterpene: A class of terpenoid composed of three isoprene units, widely found in plant essential oils with diverse biological activities.

Apoptosis: Programmed cell death characterised by chromatin condensation, membrane blebbing and caspase activation, pivotal for eliminating cancerous cells.

Cytotoxicity: The capacity of a compound to kill or inhibit the growth of cells, used to assess antitumour potency in vitro.

MAPK signalling pathway: A cascade of kinases (including ERK, JNK and p38) that regulates cell proliferation, differentiation and survival; often dysregulated in cancer.

Chemosensitisation: Enhancement of tumour cell susceptibility to chemotherapeutic agents through co-treatment, lowering effective drug doses and mitigating resistance.

References

1. β-caryophyllene sensitizes hepatocellular carcinoma cells to chemotherapeutics and inhibits cell malignancy through targeting MAPK signaling pathway. Frontiers in Pharmacology (2024).
2. Chemical Composition, Antioxidant, and Cytotoxic Activity of Essential Oils in the Above-Ground Parts of Sonchus oleraceus L.. Plants (2024).
3. β‐caryophyllene and β‐caryophyllene oxide—natural compounds of anticancer and analgesic properties. Cancer Medicine (2016).
4. β‐Caryophyllene, a Compound Isolated from the Biblical Balm of Gilead (Commiphora gileadensis), Is a Selective Apoptosis Inducer for Tumor Cell Lines. Evidence-based Complementary and Alternative Medicine (2012).
5. The Influence of Sesquiterpenes from Myrica rubra on the Antiproliferative and Pro-Oxidative Effects of Doxorubicin and Its Accumulation in Cancer Cells. Molecules (2015).