Baicalein Inhibits Proliferation, Migration, and Invasion of Mesothelioma Cells Through the p53-FOXM1 Signaling Axis

Our plain-English summary of Baicalein Inhibits Proliferation, Migration, and Invasion of Mesothelioma Cells Through the p53-FOXM1 Signaling Axis, by X.Y. Zheng, C. Guo, J. Peng, et al (Cancer Management and Research, 2025).

The study

• Authors: X.Y. Zheng, C. Guo, J. Peng, P.X. Tang, Z. Xia, W.F. Xu, X.H. Li
• Journal: Cancer Management and Research
• Published: 2025;17:3197-3209
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: Baicalein, a natural flavonoid derived from the root of Scutellaria baicalensis, has demonstrated antitumor efficacy in several cancers. However, its effects on human mesothelioma remain largely unclear. This study evaluates the antitumor roles and mechanisms of baicalein in mesothelioma cell lines.

Materials And Methods: Effects of baicalein on mesothelioma cells phenotypic changes were investigated by measuring cell proliferation, apoptosis, migration, invasion, and cell-cycle alterations. Bioinformatic methods were applied to predict the mechanisms by which baicalien mediated its antitumor roles in mesothelioma. Crucial signaling molecules among p53-FOXM1 signaling axis, including p53, FOXM1 and cyclin B1, were evaluated by immunoblotting in mesothelioma cells.

Results: Treatment with baicalein significantly inhibited mesothelioma cell viability in a dose-dependent manner, with 48 h IC50 values of 48.9 µM for MESO257 and 53.2 µM for MESO924. Baicalein also markedly reduced cell migration and invasion, while inducing apoptosis in both cell lines. Mechanistically, baicalein suppressed the p53-FOXM1 signaling axis, decreasing FOXM1 and Cyclin B1 while increasing p53 expression. Furthermore, FOXM1 overexpression attenuated the antiproliferative, anti-migratory, anti-invasive and proapoptotic effects of baicalein.

Conclusion: Baicalein suppresses mesothelioma cell growth and invasion in vitro through modulation of the p53-FOXM1 signaling axis. These findings support its potential as a lead compound for further preclinical evaluation in mesothelioma.

© 2025 Zheng et al.

In plain English

This laboratory study used two human mesothelioma cell lines, MESO257 and MESO924. The cell lines came from surgical tissue of untreated patients. The researchers treated the cells with baicalein, a natural compound from the root of Scutellaria baicalensis, and compared them with control cells. The study did not examine asbestos exposure. Baicalein lowered the readings of a cell-viability test, and higher doses had a larger effect. After 48 hours, the concentration that halved this reading compared with control cells was 48.9 µM for MESO257 and 53.2 µM for MESO924. Treated cells showed more apoptosis (programmed cell death), moved less to close a scratch, and invaded less through a gel barrier. Baicalein raised levels of the protein p53 and lowered the proteins FOXM1 and cyclin B1. When the cells were made to produce extra FOXM1, the effects of baicalein were weaker. The authors concluded that baicalein acts at least partly through the p53-FOXM1 pathway, and they called it a promising lead compound that needs further testing. They noted that laboratory cell experiments may not reflect conditions in living organisms.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on human mesothelioma cell lines, with gene-expression (bioinformatic) analysis and FOXM1 overexpression rescue experiments
• Who was studied: Two human malignant mesothelioma cell lines (MESO257 and MESO924), established from discarded surgical specimens of treatment-naïve patients, used under protocols approved by the Brigham and Women's Hospital IRB. The Methods describe both as epithelial-type; the Discussion calls MESO924 biphasic.
• Exposure: Baicalein (a plant flavonoid) at different concentrations, compared with DMSO vehicle control, mostly for 48 hours. Asbestos exposure was not studied.
• Main results:
  • Baicalein lowered cell viability, as measured by a cell proliferation assay normalized to DMSO control, in a concentration-dependent manner. After 48 hours, the IC50 values were 48.9 µM for MESO257 and 53.2 µM for MESO924. The IC50 is the concentration that halved the viability reading relative to control.
  • Baicalein at 50 µM and 100 µM significantly reduced the viability of both cell lines.
  • In both cell lines, baicalein increased the G2 peak and slightly decreased the G1/S peak in cell-cycle analysis.
  • Baicalein significantly increased caspase 3/7 activity (a marker of apoptosis) in both cell lines compared with DMSO control.
  • Baicalein significantly inhibited wound closure (migration) compared with DMSO-treated cells.
  • Baicalein reduced the invasive capability of both cell lines compared with DMSO control.
  • Of 50 hallmark gene sets analyzed, 22 were enriched after baicalein treatment.
  • Database (GPSA) analysis showed a Pearson correlation coefficient of 0.77 between baicalein and FOXM1.
  • In both cell lines, baicalein increased p53 and decreased FOXM1 and cyclin B1 protein levels in a dose-dependent manner compared with DMSO control.
  • FOXM1 overexpression reduced the antiproliferative effect of baicalein in both cell lines.
  • FOXM1 overexpression weakened the baicalein-induced suppression of migration and invasion.
• The authors' conclusion: The authors concluded that baicalein acts through the p53-FOXM1 signaling axis in mesothelioma cells in vitro. They suggested it is a promising lead compound that needs further validation in preclinical and in vivo models.
• Limitations the authors state:
  • The study focused on the p53-FOXM1 axis; other pathways and target genes may also contribute to baicalein's effects.
  • In vitro experiments may not reflect conditions in living organisms; in vivo studies are needed.
  • The proposed role of oxidative stress and DNA damage was not directly tested; it remains speculative.
  • Direct experimental evidence that baicalein inhibits the EMT pathway was not established.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Apoptosis.

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