Pharmacological Activities of Xanthones in Cancer Therapy

Xanthones are a class of tricyclic polyphenolic compounds predominantly derived from the pericarp of Garcinia species. In cancer therapy they exert a spectrum of pharmacological activities, including inhibition of tumour cell proliferation, induction of programmed cell death, suppression of metastatic spread and modulation of redox homeostasis. These effects arise from direct interactions with key signalling pathways such as PI3K/Akt, MAPKs and NF-κB, as well as from interference with metabolic enzymes like fatty acid synthase. Xanthones also promote oxidative stress in malignant cells while bolstering endogenous antioxidant defences in normal tissues through activation of the Nrf2–HO-1 axis. Emerging evidence supports their utility as adjuvant agents to enhance the efficacy of standard chemotherapeutics, to overcome drug resistance and to mitigate toxicity. Taken together, the pleiotropic actions of xanthones afford both cytotoxic and cytoprotective outcomes that underpin their promise as versatile candidates in multimodal cancer management.

Research from Nature Portfolio

Studies have illuminated the capacity of α-mangostin to protect non-malignant cells from oxidative insult through activation of the Nrf2 transcription factor. In a light-damaged retina model, α-mangostin enhanced nuclear translocation of Nrf2 and up-regulated heme oxygenase-1, superoxide dismutase and glutathione peroxidase activities, thereby reducing lipid peroxidation and apoptosis in retinal pigment epithelial cells. Complementary in vitro experiments demonstrated suppression of MAPK signalling alongside modulation of PKC-δ, indicating that redox-sensitive kinases are key mediators of xanthone-induced cytoprotection. These findings establish a mechanistic framework for harnessing xanthones to attenuate oxidative stress and preserve tissue integrity during adjunctive cancer therapies.

Pharmacological Activities of Xanthones in Cancer Therapy publication trend

The graph below shows the total number of articles in pharmacological activities of xanthones in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Apoptosis: programmed cell death involving caspase cascades and regulated removal of damaged or unwanted cells.

Reactive oxygen species (ROS): chemically reactive molecules containing oxygen that can induce cellular damage or trigger signalling pathways.

Nrf2 (NF-E2-related factor 2): a transcription factor that up-regulates antioxidant and cytoprotective genes in response to oxidative stress.

Epithelial-mesenchymal transition (EMT): a process by which epithelial cells acquire mesenchymal traits, enhancing migratory and invasive potential.

Fatty acid synthase (FAS): a multi-enzyme complex that catalyses de novo fatty acid synthesis, often up-regulated in cancer cells.

References

1. Anti-Cancer Effects of Xanthones from Pericarps of Mangosteen. International Journal of Molecular Sciences (2008).
2. Protective effect of alpha-mangostin against oxidative stress induced-retinal cell death. Scientific Reports (2016).
3. Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells. Molecular Cancer (2014).
4. Alpha-mangostin induces apoptosis through activation of reactive oxygen species and ASK1/p38 signaling pathway in cervical cancer cells. Oncotarget (2017).