Antineoplastic activity of povidone-iodine on different mesothelioma cell lines: results of in vitro study

Our plain-English summary of Antineoplastic activity of povidone-iodine on different mesothelioma cell lines: results of in vitro study, by A. Fiorelli, F. Pentimalli, V. D'Urso, et al (European Journal of Cardio-thoracic Surgery, 2014).

The study

• Authors: A. Fiorelli, F. Pentimalli, V. D'Urso, D. Di Marzo, I.M. Forte, A. Giordano, M. Di Domenico, M. Accardo, U. Di Serio, M. Santini
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2014;45(6):993-1000
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: Povidone-iodine (PVP-I) or Betadine, owing to its antineoplastic activity, is also used as an adjuvant during intra-abdominal or intrathoracic surgery. However, the protocol of PVP-I administration has not been optimized to achieve the best antitumoural efficacy. We aimed to determine the optimal concentration of PVP-I, the time of incubation and the mechanism of cell death by analysing the effect of different doses and time of administration of PVP-I on the cell viability of different mesothelioma cell lines.

Methods: Four different cell lines (MET 5A/normal mesothelium; H2052/sarcomatoid mesothelioma; ISTMES2/epithelial mesothelioma; MSTO/biphasic mesothelioma) were incubated with increasing concentrations of diluted PVP-I (0.0001; 0.001; 0.01; 0.1; 1%) for 5, 10, 30, 60 min and 24 h, respectively. Cell viability was determined using cell direct cytotoxicity assay and cell death was determined through flow cytometry assay analysis. The superoxide dismutase activity was assessed functionally through a specific inhibitor to evaluate the mechanism of cell death.

Results: The antiproliferative effect of PVP-I varied largely among different cell lines in a dose- and time-dependent manner. At 0.1% concentration for 10 min of incubation, the percentage of viable cells was 0.5 ± 0.1; 0.8 ± 0.5 and 0% (P < 0.01) for MET5A, ISTMES2 and MSTO, respectively. Conversely, the same concentration did not significantly affect the H2052 cell line which was completely suppressed at a 1% concentration of PVP-I. Double staining of Annexin V and DNA showed that PVP-I induced cell death in all four cell lines via necrosis depending on PVP-I concentration. However, H2052 was found to be more resistant than MSTO, ISTMES2 and MET 5A cells lines. The activity of superoxide dismutase was significantly inhibited in all cell lines.

Conclusions: Our results confirmed the anti-neoplastic activity of PVP-I especially on ISTMES2 and MSTO cell lines. With respect to chemotherapy pleural irrigation, washing with PVP-I is cost-effective and easy. If confirmed by larger studies, our findings suggest that the intrapleural irrigation with PVP-I (0.1% concentration for 10 min) in patients with epithelial or biphasic mesothelioma undergoing cytoreductive surgery might be applied in thoracic surgery practice to prevent neoplastic cell growth.

© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

In plain English

This was a laboratory (in vitro) study of cells grown in dishes. It did not study people or asbestos exposure. The authors tested povidone-iodine (PVP-I, also sold as Betadine), an antiseptic, on four commercially available cell lines: MET5A (normal mesothelium), H2052 (sarcomatoid mesothelioma), ISTMES2 (epithelial mesothelioma) and MSTO (biphasic mesothelioma). Cells were exposed to diluted PVP-I at concentrations from 0.0001% to 1% for times from 5 minutes to 24 hours. At 0.1% for 10 minutes, the share of cells still alive fell to 0.5 ± 0.1% for MET5A, 0.8 ± 0.5% for ISTMES2 and 0% for MSTO. The sarcomatoid H2052 cells were more resistant. At 0.1%, 84 ± 0.4% were still alive after 10 minutes. At 1%, survival fell to 0.7 ± 0.1% after 30 minutes. Dead cells were mainly in late apoptosis or necrosis. Activity of an enzyme called superoxide dismutase was reduced. PVP-I also killed the normal mesothelial cells. The authors concluded that PVP-I slowed growth of these cells. They said animal studies are needed before recommending it as a pleural wash during mesothelioma surgery.

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
• Who was studied: Four commercially available cell lines: MET5A (normal mesothelium), H2052 (sarcomatoid mesothelioma), MSTO (biphasic mesothelioma) and ISTMES2 (epithelial mesothelioma)
• Exposure: Povidone-iodine (PVP-I) diluted to 0.0001%, 0.001%, 0.01%, 0.1% or 1%, applied for 5, 10, 30 or 60 minutes or 24 hours. No asbestos exposure was studied.
• Main results:
  • For MET5A, ISTMES2 and MSTO cells, the shortest exposure giving a strong killing effect (less than 1% of cells still alive) was 10 minutes at 0.1%
  • At 0.1%, cells still alive after 10 minutes versus 5 minutes were 0.5 ± 0.1 vs 5.2 ± 0.8% for MET5A, 0.8 ± 0.5 vs 5.3 ± 0.5% for ISTMES2, and 0 vs 2.1 ± 0.1% for MSTO (each P less than 0.05)
  • The sarcomatoid H2052 cells were not significantly affected by 0.1%: 84 ± 0.4% were still alive after 10 minutes, and 58 ± 0.9% after 24 hours
  • At 1%, H2052 survival was 3.4 ± 0.2% after 5 minutes, 2.2 ± 0.1% after 10 minutes and 0.7 ± 0.1% after 30 minutes
  • In flow cytometry at 0.1%, 58% of H2052 cells were still alive, compared with less than 1% for the other three lines. Among H2052 cells, 33% were in late apoptosis or necrosis and 6% in early apoptosis. Dead cells in all lines were mainly late apoptotic or necrotic.
  • Superoxide dismutase activity was significantly reduced at 0.1% compared with lower concentrations in all four cell lines. For H2052, 1% also differed significantly from 0.1%.
• The authors' conclusion: The authors concluded that low doses and short exposures of PVP-I slowed growth of these mesothelioma cells by causing cell death, with H2052 the most resistant. They said animal studies should confirm this before intraoperative pleural lavage with PVP-I is recommended.
• Limitations the authors state:
  • Commercial cell lines may respond differently from human mesotheliomas. It is not known whether the results hold in living organisms.
  • PVP-I also reduced growth of the normal mesothelial cells
  • PVP-I might be toxic to other tissues
  • In the published conference discussion, the presenting author said the flat (planar) cell model could not show how deeply PVP-I penetrates tissue

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, Intrathoracic, Mesothelium, Sarcomatoid, Biphasic Mesothelioma, Superoxide, Necrosis, Chemotherapy.

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