Quantitative evaluation of cellular uptake, DNA incorporation and adduct formation in cisplatin sensitive and resistant cell lines: Comparison of different Pt-containing drugs

Biochemical Pharmacology
M Corte-RodríguezA Sanz-Medel

Abstract

The use of Pt-containing compounds as chemotherapeutic agents facilitates drug monitoring by using highly sensitive elemental techniques like inductively coupled plasma mass spectrometry (ICP-MS). However, methodological problems arise when trying to compare different experiments due to the high variability of biological parameters. In this work we have attempted to identify and correct such variations in order to compare the biological behavior of cisplatin, oxaliplatin and pyrodach-2 (a novel platinum-containing agent). A detailed study to address differential cellular uptake has been conducted in three different cell lines: lung adenocarcinoma (A549); cisplatin-sensitive ovarian carcinoma (A2780); and cisplatin-resistant ovarian carcinoma (A2780cis). The normalization of Pt results to cell mass, after freeze-drying, has been used to minimize the errors associated with cell counting. Similarly, Pt accumulation in DNA has been evaluated by referencing the Pt results to the DNA concentration, as measured by (31)P monitoring using flow-injection and ICP-MS detection. These strategies have permitted to address significantly lower Pt levels in the resistant cells when treated with cisplatin or oxaliplatin as well as an independent...Continue Reading

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Citations

May 1, 2020·Bioinorganic Chemistry and Applications·M Florencia MosquilloLeticia Pérez-Díaz
Jun 17, 2020·Journal of Cellular and Molecular Medicine·Lumin ChenWei-Chun Chang
Jul 28, 2019·International Journal of Molecular Sciences·Paul NoordhuisGodefridus J Peters
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May 11, 2018·Chemical Biology & Drug Design·M Florencia MosquilloLeticia Pérez-Díaz
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Jun 3, 2021·International Journal of Molecular Sciences·Hadar Golan BermanSheera Adar
Jul 10, 2019·Journal of the American Chemical Society·Alessia LasorsaFabio Arnesano

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