The Traditional Chinese Medicine Formula Modified Wu Bao San Induces Cell Cycle Arrest and Apoptosis through Restoration of Retinoblastoma Protein Function and Inhibition of Aurora Kinase Activity

TL;DR

This study shows that a traditional Chinese medicine formula, Modified Wu Bao San, fights cancer by stopping cell division and restoring a key tumor suppressor protein.

Contribution

The study identifies Aurora kinase inhibition and Rb protein restoration as novel molecular mechanisms of Modified Wu Bao San's anticancer effects.

Findings

MWBSE induces cytokinesis failure by inhibiting Aurora kinase activity.

MWBSE reduces Rb phosphorylation, restoring its tumor-suppressing function and causing cell cycle arrest.

Abstract

Background: Traditional Chinese Medicine (TCM) has a long-standing history in treating various diseases, including cancer. Wu Bao San is a traditional formula known for its ability to clear heat, detoxify, relieve cough and phlegm and treat tumours. The modified Wu Bao San (MWBS) is a conventional medicine prescribed by doctors of Chinese medicine. However, the molecular mechanisms underlying the anticancer effects remain unclear owing to the complexity of the components of traditional Chinese medicine, making it challenging to pinpoint specific molecular targets or pathways underlying their clinical effect.

Methods: In this study, we used an MTT assay, flow cytometry, indirect immunofluoresence imaging, and western blotting to analyse the viability, cell cycle profiles, morphology, and protein levels of cells after MWBSE treatment.

Results: Our results showed that MWBSE has multiple anticancer effects. First, MWBSE induces cytokinesis failure by inhibiting Aurora kinase, leading cells to commit to cell death. Additionally, MWBSE reduces the phosphorylation of Rb, restoring its function and resulting in cell cycle arrest. The overexpression of Aurora kinases plays a pivotal role in sustaining malignant cell behaviors such as uncontrolled growth, colony formation, and tumor development. The retinoblastoma protein (Rb) is a key tumor suppressor that regulates the cell cycle, particularly the transition from the G1 to the S phase due to its significant involvement in tumor biology. Aurora kinases and Rb have emerged as promising targets for cancer therapy.

Conclusion: Our findings provide a mechanistic explanation of the targets and anti-tumor pathways of MWBSE.

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