Reduced cell viability and apoptosis induction in human thyroid carcinoma and mesothelioma cells exposed to cidofovir

Our plain-English summary of Reduced cell viability and apoptosis induction in human thyroid carcinoma and mesothelioma cells exposed to cidofovir, by S. Catalani, F. Palma, S. Battistelli, et al (Toxicology in Vitro, 2017).

The study

• Authors: S. Catalani, F. Palma, S. Battistelli, B. Nuvoli, R. Galati, S. Benedetti
• Journal: Toxicology in Vitro
• Published: 2017;41:49-55
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Besides its well-recognized antiviral activity, Cidofovir (CDV) has been shown to exert anticancer properties both within in vitro and in vivo models. The aim of this study was to evaluate the effects of CDV on still unexplored cultured cancer cells from human mesothelioma as well as breast, colon, liver, lung, prostate, and thyroid carcinomas. Overall, a dose- and time-dependent inhibition of cell viability was observed after CDV exposure. To clarify the mechanisms underlying CDV action, apoptotic cell death was investigated in two infected cell lines [Ist-Mes1 and Ist-Mes2 mesothelioma cells (SV40+)] and in two uninfected cell lines (NCI-H2425 mesothelioma cells and FTC-133 thyroid cancer cells), which resulted the most sensitive to CDV treatment. Reduced expression of procaspase-3 and increased expression of PARP p85 fragment were observed in both infected and uninfected mesothelioma cells, indicating apoptosis induction by CDV in a virus-independent manner. Similarly, the increase of the pro-apoptotic proteins p53, cytochrome c and caspase-3, the decrease of the survival protein Bcl-x, and the increment of Bax/Bcl-2 ratio revealed the occurrence of apoptosis in CDV-treated FTC-133. The presence of nuclear DNA fragmentation confirmed apoptotic cell death by CDV. Overall, our findings warrant further investigations to explore the therapeutic potential of CDV for human mesothelioma and follicular thyroid carcinoma.

Copyright © 2017 Elsevier B.V. All rights reserved.

In plain English

This laboratory study tested cidofovir, an antiviral drug, on human cancer cells grown in culture, not on patients. The authors treated ten cancer cell lines with doses from 10 to 1000 µM for up to 120 hours. Three were mesothelioma lines: two carried the virus SV40 and one did not. The others came from breast, cervix, colon, liver, lung, prostate and thyroid cancers. Measured cell viability fell as dose and exposure time increased. The mesothelioma cells were the most sensitive. After 120 hours, the concentration that halved measured viability was 23 to 34 µM for the three mesothelioma lines. In mesothelioma cells with and without SV40, protein changes indicated apoptosis (programmed cell death). In follicular thyroid carcinoma cells (FTC-133), pretreatment with 100 µM cidofovir for 24 hours reduced colony formation by 55% compared with untreated cells. Cidofovir at 100 µM also produced protein changes and DNA fragmentation consistent with apoptosis in these cells. The authors concluded that cidofovir reduced cancer cell viability and induced apoptosis independently of viral infection. They concluded that its therapeutic potential for mesothelioma and follicular thyroid carcinoma warrants further investigation.

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 cultured human cancer cell lines
• Who was studied: Ten human cancer cell lines. Three were mesothelioma lines: NCI-H2452 (SV40-negative) and Ist-Mes1 and Ist-Mes2 (SV40-positive). The others were HeLa cervix carcinoma (HPV18-positive), FTC-133 follicular thyroid carcinoma, Hep-G2 liver, MDA-MB-231 breast, NCI-H1975 lung, PC-3 prostate and Caco-2 colorectal. The work was done at the University of Urbino and the Regina Elena National Cancer Institute, Rome, Italy.
• Exposure: The antiviral drug cidofovir (CDV) at doses from 10 to 1000 µM for up to 120 hours. Untreated cells receiving PBS served as controls. No asbestos exposure was studied.
• Main results:
  • Across the cell lines, cell viability fell as the cidofovir dose and exposure time increased. Viability was measured with the WST-8 assay, which detects enzyme activity in viable cells.
  • Judged by the concentration that halved measured viability (IC50), the mesothelioma cells were the most sensitive. At 120 hours the IC50 values were 23 µM for NCI-H2452, 34 µM for Ist-Mes1 and 27 µM for Ist-Mes2.
  • In mesothelioma cells with SV40 (Ist-Mes1, Ist-Mes2) and without it, 120 hours of cidofovir at 10 µM decreased procaspase-3 and increased PARP p85 fragment. The authors interpreted this as apoptosis that did not depend on the virus.
  • Among the carcinoma lines without a virus, FTC-133 thyroid carcinoma cells were the most sensitive and Caco-2 colorectal cells the most resistant. Among all carcinoma lines, HPV18-positive HeLa cells were the most responsive.
  • FTC-133 cells were pretreated with cidofovir for 24 hours. At 100 µM, colony formation fell by 55% compared with untreated cells.
  • In FTC-133 cells after 96 hours at 100 µM, compared with untreated cells, pro-apoptotic proteins rose: cytochrome c by 130%, phospho-p53 (S15) by 49% and cleaved caspase-3 by 46%. The anti-apoptotic protein Bcl-x fell by 57%.
  • FTC-133 cells showed nuclear DNA fragmentation after 96 and 120 hours with cidofovir at 100 µM.
  • Daily microscope checks found no changes suggesting primary necrosis.
• The authors' conclusion: The authors concluded that cidofovir reduced the viability of human mesothelioma and follicular thyroid carcinoma cells in vitro and induced apoptosis independently of viral infection. They concluded that its therapeutic potential for these cancers warrants further investigation.

Topics

Medical terms in this study, explained in our Lexicon: Apoptosis, Carcinoma, Mesothelioma, SV40.

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