Exploration of the anticancer properties of Caffeic Acid in malignant mesothelioma cells

Our plain-English summary of Exploration of the anticancer properties of Caffeic Acid in malignant mesothelioma cells, by D. Muratoglu, G. Turhal, B. Demirkan, et al (Medical Oncology, 2025).

The study

• Authors: D. Muratoglu, G. Turhal, B. Demirkan, I.N. Baslilar, N.S. Yuncu, A. Demiroglu-Zergeroglu
• Journal: Medical Oncology
• Published: 2025;42(7):249
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant Pleural Mesothelioma (MPM) is the most prevalent type of Mesothelioma and currently has no effective treatment options. This underscores the urgent need to explore new therapeutic agents and innovative strategies. Phenolic acids are significant natural compounds recognised for their effectiveness in treating various diseases, including cancer. This study evaluates the anti-carcinogenic properties of Cinnamic acid (CINN) and its derivative Caffeic acid (CA) in both MPM and non-cancerous mesothelial cells. Results show that CA exhibited greater efficiency than CINN in reducing cancer cell survival. This enhanced efficacy is primarily attributed to CA's higher selectivity index and its ability to inhibit proliferation at lower concentrations. Consequently, further analysis was conducted using CA. The subsequent findings revealed that CA suppressed proliferative markers, Ki67 and PCNA, inhibited colony formation and wound healing in MM cells. Experiments also exposed that it suppresses the phosphorylation of ERK1/2 and AKT proteins in a concentration-dependent manner, while the phosphorylation of STAT3 remains unaffected. The pattern of protein phosphorylation and expression suppression by CA in 3D cells resembles that in 2D cells, although it occurred at higher concentrations. Additionally, CA significantly enhanced the expression of p53-regulated proteins p21 and p27, resulting in G2/M arrest in both SPC111 and SPC212 cell lines. Moreover, elevated concentrations of CA were associated with an increased number of dead cells, as demonstrated by DAPI/PI and AO/EtBr fluorescence staining. The increased Bax/Bcl-2 protein ratio, and BH3-only proteins (Bik and PUMA) and the cleavage of caspase-3 indicated that CA induces mitochondrial apoptosis. Our research with MM cells and three-dimensional micro-tumours suggests that CA may be a promising alternative for future MM therapies. However, it is vital to conduct high-throughput in vivo studies to elucidate further the potential importance of CA in treating this devastating disease.

© 2025. The Author(s).

In plain English

This was a laboratory study of cells grown in dishes. No patients or animals were studied, and asbestos exposure was not tested. The authors treated two malignant pleural mesothelioma (MPM) cell lines, SPC111 and SPC212, and a non-cancerous mesothelial cell line, MeT-5A, with two plant compounds: cinnamic acid (CINN) and caffeic acid (CA). CA had higher selectivity index values than CINN (2.74 and 2.64 versus 1.43 and 1.16, in SPC111 and SPC212 respectively). CA reduced cancer cell numbers from 100 µM, compared with about 400 µM in non-cancerous cells, so later tests used CA only. In the cancer cells, CA lowered markers of cell division. It reduced colony formation and delayed wound closure, significantly from 50 µM. It stalled cells at the G2/M phase of the cell cycle and increased cell death, with protein changes the authors read as mitochondrial apoptosis. Three-dimensional cell clusters needed about twice the concentration for the same signalling effect. The authors concluded that CA may be a promising option for future mesothelioma therapies and that the findings next need testing in vivo.

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 cultured cell lines, including 2D monolayers and 3D spheroids
• Who was studied: Commercially obtained cell lines: non-cancerous mesothelial MeT-5A cells and the MPM cell lines SPC111 and SPC212. SPC111 and SPC212 were also grown as 3D spheroids. Each experiment was done three times.
• Exposure: Cinnamic acid (0–5000 µM) and caffeic acid (0–3000 µM) for 72 h in viability tests. Later tests used caffeic acid only, mostly at 25–100 µM (up to 200 µM in spheroids), for 24 h. Asbestos exposure was not studied.
• Main results:
  • Selectivity index in SPC111 and SPC212 cells: 1.43 and 1.16 for CINN; 2.74 and 2.64 for CA
  • CA reduced non-cancerous MeT-5A cell numbers from about 400 µM, but reduced MPM cancer cell numbers from 100 µM
  • CA-treated MPM cells showed lower levels of the proliferation markers Ki-67 and PCNA
  • Colony numbers fell as CA concentration rose, with a significant effect at 50 µM in both SPC111 and SPC212 cells. Wound closure was delayed at 50 µM and above.
  • 3D spheroids shrank significantly at 200 µM CA
  • CA significantly suppressed ERK1/2 and AKT phosphorylation at 100 µM in monolayer cells. Spheroid cells needed twice that concentration.
  • CA did not affect STAT3 phosphorylation or expression in either cell line, in 2D or 3D
  • Accumulation of MPM cells at the G2/M phase increased significantly from 50 µM CA in 24 h. p21 and p27 rose at 50 µM or more.
  • Dead cells increased significantly at 100 µM CA in AO/EtBr staining
  • Bcl-2 decreased and Bax increased. The authors described this as strongly suggesting mitochondrial apoptosis, and activated caspase-3 appeared at 100 µM CA.
• The authors' conclusion: The authors concluded that, based on their work with MM cells and 3D micro-tumours, CA may be a promising alternative for future MM therapies. They added that the findings still need to be validated in vivo.
• Limitations the authors state:
  • The findings come from cultured cells only and have not yet been validated in vivo
  • The effect of millimolar CA concentrations on STAT3 was reported without the data being shown

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Carcinogenic, Mesothelial Cells, Apoptosis.

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