Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation

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2014
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Bergadà Bertran, Laura
Yeramian Hakim, Andree
Sorolla Bardají, Anabel
Matias-Guiu, Xavier
Dolcet Roca, Xavier
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Bergadà Bertran, Laura; Yeramian Hakim, Andree; Sorolla Bardají, Anabel; Matias-Guiu, Xavier; Dolcet Roca, Xavier; . (2014) . Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation. PLoS One, 2014, vol. 9, núm. 3, e92764. https://doi.org/10.1371/journal.pone.0092764.
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Abstract
We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.
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http://hdl.handle.net/10459.1/48326
DOI
https://doi.org/10.1371/journal.pone.0092764
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PLoS One, 2014, vol. 9, núm. 3, e92764
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cc-by, (c) Bergadà et al., 2014
Except where otherwise noted, this item's license is described as cc-by, (c) Bergadà et al., 2014