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Resveratrol Affects Cell Activities, Induces Apoptosis and Regulates AMPK Signaling Pathway in Pleural Mesothelioma

Maria Rosa Iaquinta1, Raffaella De Pace2, Assia Benkhalqui1,3

  • 1Department of Medical Sciences, Laboratories of Cell Biology and Molecular Genetics, University of Ferrara, Ferrara, Italy.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|October 19, 2025
PubMed

Insights

Resveratrol (RSV) shows promise as a therapeutic adjuvant for malignant pleural mesothelioma (PM). This natural compound effectively inhibits PM cell viability, migration, and proliferation, offering new avenues for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Malignant pleural mesothelioma (PM) is an aggressive cancer with limited treatment options.
  • Resveratrol (RSV), a natural polyphenol, has demonstrated anti-cancer properties.
  • The potential of RSV as an adjuvant therapy for PM requires further investigation.

Purpose of the Study:

  • To evaluate the efficacy of resveratrol (RSV) as a tumor suppressor and adjuvant agent in malignant pleural mesothelioma (PM) cell lines.
  • To investigate the molecular mechanisms underlying RSV's effects on PM cells.
  • To assess RSV's impact on cell viability, apoptosis, migration, and signaling pathways.

Main Methods:

  • Treatment of PM cell lines (MSTO-211H and IST-MES 2) with RSV.
  • Assessment of cell viability using MTT assay and Live/Dead staining.
  • Analysis of apoptosis via Annexin V-PI and Caspase-3/7 staining.
  • Evaluation of cell migration, E-cadherin expression, and β-catenin localization.
  • Measurement of intracellular calcium levels.
  • Gene expression analysis of key cellular pathways including Wnt/β-catenin and AMPK signaling.

Main Results:

  • RSV significantly decreased viability and induced apoptosis in PM cell lines, particularly MSTO-211H.
  • RSV inhibited the migration ability of both PM cell lines.
  • RSV treatment affected cellular morphology, reduced E-cadherin expression, and decreased nuclear β-catenin, indicating attenuation of Wnt/β-catenin signaling.
  • RSV modulated gene expression related to cellular adhesion, proliferation, metabolic activity, and AMPK signaling.
  • RSV reduced mitochondrial and cytoplasmic calcium levels in IST-MES 2 cells.

Conclusions:

  • Resveratrol demonstrates significant anti-tumor effects against malignant pleural mesothelioma cells.
  • RSV acts as a potential adjuvant agent, inhibiting proliferation, inducing apoptosis, and reducing migration.
  • RSV's mechanism involves the modulation of key signaling pathways, including Wnt/β-catenin and AMPK, making it a promising candidate for PM therapy.
Keywords:
AMPKapoptosiscell growth inhibitioninvasionpleural mesothelioma (PM)resveratrol (RSV)

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