How a natural compound may fight aggressive breast cancer

Jenn Hoskins
2nd December, 2025

How a natural compound may fight aggressive breast cancer

Research workflow diagram from study.

Image adapted from: Zhao et al. / CC BY (Source)

Key Findings

  • This study, conducted in China, investigated oridonin, a natural compound, as a potential treatment for triple-negative breast cancer (TNBC)
  • The research suggests oridonin works by disrupting key signaling pathways in TNBC cells, notably the PI3K/Akt pathway and interactions with proteins like AKT1, EGFR, and SRC
  • Computational modeling indicates oridonin strongly binds to several proteins crucial for cancer development, potentially inhibiting TNBC growth and spread
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer lacking the common receptors – estrogen, progesterone, and HER2 – found in other types of breast cancer[2]. This absence means standard hormone therapies are ineffective, leaving patients with limited treatment options and, historically, a poorer prognosis. TNBC is also disproportionately diagnosed in younger women and Black women[2]. Despite improvements in chemotherapy and immunotherapy, the need for targeted therapies remains critical, as the term “triple-negative” itself highlights the lack of specific drug targets[2]. The biological complexity of TNBC, with its diverse genetic and molecular profiles, further complicates treatment strategies[3]. Researchers at Pu’er People’s Hospital & Fujian Provincial Hospital, China, have recently investigated the potential of oridonin, a natural compound derived from the plant Rabdosia rubescens, as a possible treatment for TNBC[1]. Oridonin has shown promise in treating various cancers and inflammatory conditions, but its specific effects on TNBC were previously unclear. This study aimed to understand how oridonin works at a molecular level to combat TNBC. The study employed a “network pharmacology” approach. This involves identifying potential targets within cancer cells that oridonin might interact with, and then mapping out how these interactions could disrupt the cancer’s growth and spread. The researchers began by using databases to identify 549 genes potentially affected by oridonin. They then narrowed this down to 106 genes specifically linked to TNBC. These genes were then used to create a network showing how the proteins they code for interact with each other – a protein-protein interaction (PPI) network. Further analysis revealed that oridonin’s effects likely center around two key areas: the PI3K/Akt signaling pathway and proteoglycans in cancer. The PI3K/Akt pathway is a crucial signaling route within cells that controls growth, survival, and metabolism. It is often overactive in cancer, driving uncontrolled cell proliferation[4]. Proteoglycans are molecules found on cell surfaces and in the surrounding environment, and they play a role in cancer progression. To confirm these findings, the researchers used a technique called molecular docking. This simulates how well oridonin binds to specific proteins within these pathways. The results showed that oridonin had a strong binding affinity for AKT1, a key protein in the PI3K/Akt pathway (binding energy of -11.40 kcal/mol). It also showed significant binding to other important proteins like EGFR, NFKB1, MAPK1, and SRC, all of which are involved in cancer development and progression. This research builds on previous work exploring natural compounds as potential treatments for TNBC[4]. Traditional Chinese Medicine (TCM) and natural medicines, with their ability to target multiple pathways simultaneously, offer a promising avenue for developing new therapies with fewer side effects[4]. The study suggests that oridonin’s ability to disrupt the PI3K/Akt pathway, alongside its interactions with other key proteins, could effectively inhibit the growth, proliferation, and spread of TNBC cells. Interestingly, a separate study demonstrated that oridonin can induce endoplasmic reticulum (ER) stress and activate TP53, ultimately leading to cancer cell death in colorectal cancer[5]. While the current study doesn’t directly investigate ER stress in TNBC, the shared mechanism of TP53 activation and disruption of cellular homeostasis suggests a potential overlap in oridonin’s anti-cancer effects across different cancer types. The inhibition of TCF4, identified in the colorectal cancer study[5], could also be a relevant mechanism in TNBC, potentially influencing the effectiveness of oridonin.

MedicineGeneticsBiochem

References

Main Study

1) Investigating the mechanism of oridonin against triple-negative breast cancer based on network pharmacology and molecular docking

Published 1st December, 2025

https://doi.org/10.1371/journal.pone.0332697

Related Studies

2) Triple negative breast cancer: Pitfalls and progress.

https://doi.org/10.1038/s41523-022-00468-0

3) Pathogenesis of Triple-Negative Breast Cancer.

https://doi.org/10.1146/annurev-pathol-042420-093238

4) The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer.

https://doi.org/10.1016/j.jep.2020.113249

5) Oridonin promotes endoplasmic reticulum stress via TP53-repressed TCF4 transactivation in colorectal cancer.

https://doi.org/10.1186/s13046-023-02702-4


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