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Interactions of cisplatin and daunorubicin at the chromatin level

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Abstract
Unexpectedly, the widely used anticancer agents Cisplatin (Cis-Pt) and Daunorubicin (Dauno) exhibited cell type- and concentration-dependent synergy or antagonism in vitro. We attempted to interpret these effects in terms of the changes elicited by the drugs in the chromatin, the target held primarily responsible for the cytotoxicity of both agents. We measured the effect of Cis-Pt on the levels of Dauno in different cell compartments, the effect of Cis-Pt on Dauno-induced nucleosome eviction, and assessed the influence of Dauno on DNA platination in flow- and laser scanning cytometry as well as in laser ablation-inductively coupled plasma-mass spectrometry assays. We show that the two drugs antagonize each other through a decrease of interstrand crosslinks upon co-treatment with Dauno, and also via the diminished Dauno uptake in the presence of Cis-Pt, and both effects are observed already at low Dauno concentrations. At high Dauno concentrations synergy becomes dominant because histone eviction by Dauno intercalation into the DNA is enhanced in the presence of co-treatment with Cis-Pt. These interactions may have an impact on the efficacy of combination treatment protocols, considering the long retention time of DNA adducts formed by both agents.
Keywords
Multidisciplinary, INTERSTRAND CROSS-LINKING, ANTHRACYCLINE ANTIBIOTICS, IN-VITRO, DNA, CELLS, CHEMOTHERAPY, CANCER, COMBINATION, DOXORUBICIN, INHIBITION

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MLA
Firouzi Niaki, Erfaneh, et al. “Interactions of Cisplatin and Daunorubicin at the Chromatin Level.” SCIENTIFIC REPORTS, vol. 10, 2020, doi:10.1038/s41598-020-57702-7.
APA
Firouzi Niaki, E., Van Acker, T., Imre, L., Nánási, P. J., Tarapcsák, S., Bacsó, Z., … Szabó, G. (2020). Interactions of cisplatin and daunorubicin at the chromatin level. SCIENTIFIC REPORTS, 10. https://doi.org/10.1038/s41598-020-57702-7
Chicago author-date
Firouzi Niaki, Erfaneh, Thibaut Van Acker, László Imre, Péter Jr. Nánási, Szabolcs Tarapcsák, Zsolt Bacsó, Frank Vanhaecke, and Gábor Szabó. 2020. “Interactions of Cisplatin and Daunorubicin at the Chromatin Level.” SCIENTIFIC REPORTS 10. https://doi.org/10.1038/s41598-020-57702-7.
Chicago author-date (all authors)
Firouzi Niaki, Erfaneh, Thibaut Van Acker, László Imre, Péter Jr. Nánási, Szabolcs Tarapcsák, Zsolt Bacsó, Frank Vanhaecke, and Gábor Szabó. 2020. “Interactions of Cisplatin and Daunorubicin at the Chromatin Level.” SCIENTIFIC REPORTS 10. doi:10.1038/s41598-020-57702-7.
Vancouver
1.
Firouzi Niaki E, Van Acker T, Imre L, Nánási PJ, Tarapcsák S, Bacsó Z, et al. Interactions of cisplatin and daunorubicin at the chromatin level. SCIENTIFIC REPORTS. 2020;10.
IEEE
[1]
E. Firouzi Niaki et al., “Interactions of cisplatin and daunorubicin at the chromatin level,” SCIENTIFIC REPORTS, vol. 10, 2020.
@article{8644501,
  abstract     = {Unexpectedly, the widely used anticancer agents Cisplatin (Cis-Pt) and Daunorubicin (Dauno) exhibited cell type- and concentration-dependent synergy or antagonism in vitro. We attempted to interpret these effects in terms of the changes elicited by the drugs in the chromatin, the target held primarily responsible for the cytotoxicity of both agents. We measured the effect of Cis-Pt on the levels of Dauno in different cell compartments, the effect of Cis-Pt on Dauno-induced nucleosome eviction, and assessed the influence of Dauno on DNA platination in flow- and laser scanning cytometry as well as in laser ablation-inductively coupled plasma-mass spectrometry assays. We show that the two drugs antagonize each other through a decrease of interstrand crosslinks upon co-treatment with Dauno, and also via the diminished Dauno uptake in the presence of Cis-Pt, and both effects are observed already at low Dauno concentrations. At high Dauno concentrations synergy becomes dominant because histone eviction by Dauno intercalation into the DNA is enhanced in the presence of co-treatment with Cis-Pt. These interactions may have an impact on the efficacy of combination treatment protocols, considering the long retention time of DNA adducts formed by both agents.},
  articleno    = {1107},
  author       = {Firouzi Niaki, Erfaneh and Van Acker, Thibaut and Imre, László and Nánási, Péter Jr. and Tarapcsák, Szabolcs and Bacsó, Zsolt and Vanhaecke, Frank and Szabó, Gábor},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keywords     = {Multidisciplinary,INTERSTRAND CROSS-LINKING,ANTHRACYCLINE ANTIBIOTICS,IN-VITRO,DNA,CELLS,CHEMOTHERAPY,CANCER,COMBINATION,DOXORUBICIN,INHIBITION},
  language     = {eng},
  pages        = {12},
  title        = {Interactions of cisplatin and daunorubicin at the chromatin level},
  url          = {http://dx.doi.org/10.1038/s41598-020-57702-7},
  volume       = {10},
  year         = {2020},
}

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