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

Our plain-English summary of Resveratrol Affects Cell Activities, Induces Apoptosis and Regulates AMPK Signaling Pathway in Pleural Mesothelioma Cells, by M.R. Iaquinta, R. De Pace, A. Benkhalqui, et al (FASEB Journal, 2025).

The study

• Authors: M.R. Iaquinta, R. De Pace, A. Benkhalqui, C. Pesaresi, S. Patergnani, G. Righes, P. Pinton, M. Tognon, F. Martini, E. Mazzoni
• Journal: FASEB Journal
• Published: 2025;39(20):e71120
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pleural Mesothelioma (PM) is an aggressive tumor with a poor prognosis and limited therapeutic options. Despite the notion that resveratrol (RSV) significantly inhibits the growth of PM cancer cells, it is necessary to evaluate the effects of this stilbene as a tumor suppressor agent. In this work, the effects of the natural polyphenol were investigated on PM cell lines (MSTO-211H and IST-MES 2) to evaluate its action as a potential adjuvant agent, together with chemotherapy. Our results showed that RSV treatment was effective in PM cell lines, in particular in MSTO-211H. RES treatment decreases the viability evaluated with the MTT assay and Live/Dead staining. RSV stimulates the apoptotic process with positive staining for Annexin V-PI and Caspase-3/7 and inhibits the migration ability of both PM cell lines. In IST-MES 2, RSV causes a reduction in mitochondrial and cytoplasmic calcium levels. Moreover, RSV affects cellular morphology, E-cadherin protein expression, and decreased nuclear localization of β-catenin, attenuating Wnt/β-catenin signaling, which regulates tumor cell proliferation. At the molecular level, RSV modulated the expression of key genes that play an important role in cellular adhesion, proliferation, and metabolic activity, as well as AMPK signaling. RSV seems to be a promising therapeutic adjuvant agent for PM treatment.

© 2025 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

In plain English

This laboratory study on cells grown in dishes involved no people or animals and did not study asbestos. The authors tested resveratrol, a plant compound, on two human pleural mesothelioma cell lines, MSTO-211H (biphasic) and IST-MES 2 (epithelioid), and on normal human mesothelial cells. Resveratrol at 1 to 1000 μM reduced growth of both cancer cell lines over 24 to 72 hours. At 100 μM, the dose used in later tests, no statistically significant change in normal-cell growth was detected. At 100 μM, resveratrol increased apoptosis (programmed cell death) markers and reduced closure of a scratch in the cell layer. The authors attributed this mainly to reduced movement at 24 hours and increasingly to reduced growth later. In IST-MES 2 cells, resveratrol also lowered calcium levels measured after histamine stimulation. In both cell lines it changed the expression of adhesion and energy-metabolism genes, including AMPK signaling genes. The authors noted that 100 μM exceeds blood levels achievable in humans and that clinical trials are needed. The authors concluded that resveratrol could be considered a novel adjuvant treatment for pleural mesothelioma, particularly the biphasic type.

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: In vitro laboratory experiment on human cell lines
• Who was studied: Two human pleural mesothelioma cell lines: MSTO-211H (biphasic histotype) and IST-MES 2 (epithelioid histotype). Human mesothelial cells (HMC) served as non-cancer comparison cells. No patients were studied.
• Exposure: Resveratrol (RSV) at concentrations of 1 to 1000 μM for 24, 48 and 72 h, with 100 μM used for most experiments. Asbestos exposure was not studied.
• Main results:
  • Resveratrol reduced proliferation (MTT assay) in both mesothelioma cell lines.
  • At 48 h, viability measured by MTT was reduced by about 50% in both mesothelioma cell lines.
  • In normal human mesothelial cells (HMC), resveratrol at 100 μM produced no statistically significant change in proliferation compared with control (p greater than 0.05).
  • In both cell lines, resveratrol at 100 μM for 48 h increased the number of cells positive for activated caspase-3/7, a marker of apoptosis, compared with untreated cells. Annexin V staining was also observed.
  • In IST-MES 2 cells, 24 h after 100 μM resveratrol, mitochondrial calcium uptake in response to histamine stimulation was reduced (p less than 0.0001), and cytoplasmic calcium was also decreased (p less than 0.05). Calcium could not be measured in MSTO-211H cells, which were more sensitive to resveratrol.
  • In a wound-healing assay, resveratrol inhibited the ability of cells in both cell lines to close the gap. The authors interpreted the 24 h result as mainly a migration effect, the 48 h result as partly due to reduced proliferation, and the 72 h wound widening as primarily due to the antiproliferative action.
  • In the extracellular matrix and adhesion gene expression array, 17 genes changed in MSTO-211H (8 up, 9 down) and 21 changed in IST-MES 2 (9 up, 12 down).
  • In the AMPK signaling gene expression array, 15 genes changed in IST-MES 2 (7 up, 8 down) and 15 changed in MSTO-211H (2 up, 13 down).
  • Immunofluorescence suggested that resveratrol blocked movement of β-catenin into the nucleus in IST-MES 2 cells. Resveratrol also influenced E-cadherin in that cell line.
  • In MSTO-211H cells, resveratrol combined with the A3 adenosine receptor agonist Cl-IB-MECA (1 nM) increased pro-apoptotic markers compared with Cl-IB-MECA alone. These data are in a supplementary figure that is not included in the text.
• The authors' conclusion: The authors concluded that resveratrol could be considered a novel adjuvant treatment for pleural mesothelioma, particularly for the biphasic histotype.
• Limitations the authors state:
  • The 100 μM concentration used exceeds the blood plasma levels achievable in humans.
  • At 48 to 72 h, reduced wound closure partly reflects reduced cell growth rather than reduced migration alone.
  • Well-controlled clinical trials with larger patient groups are needed to prove efficacy in cancer patients.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

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

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