Abstract
The objective of this study was to regulate the cytotoxicity of cisplatin (cisPt) minimizing its adverse effects. For this purpose, the lowest cisPt concentration needed to obtain a significant positive response in cutaneous squamous cell carcinoma (cSCC) was explored. Two adjuvant agents as gold nanoparticles (AuNP) and chelating tricine were tested as enhancers in cisPt treatment. Effectiveness of all treatments was assessed by means of biochemical techniques, which offer quantitative data, as well as two microscopy–based techniques that provided qualitative cell imaging. The present work confirms the effectiveness of free cisplatin at very low concentrations. In order to enhance its effectiveness while the side effects were probably diminished, cisPt 3.5 μM was administered with AuNP 2.5 mM, showing an effectiveness practically equal to that observed with free cisPt. However, the second treatment investigated, based on cisPt 3.5 μM combined with tricine 50 mM, enhanced drug effectiveness, increasing the percentage of cells dying by apoptosis. This treatment was even better in terms of cell damage than free cisPt at 15 μM. Images obtained by TEM and cryo-SXT confirmed these results, since a notable number of apoptotic bodies were detected when cisPt was combined with tricine. Thus, tricine was clearly a better adjuvant for cisPt treatments.
Highlights
Cis-diamminedichloroplatinum (II) is an alkylating neutral complex, widely used as a chemotherapeutic agent against a broad range of cancers, showing substantial therapeutic impact against most carcinoma-like tumors [1,2]
Cells were treated at three cisPt concentrations 3.5, 7 and 15 μM in order to determine the effect of cisPt at very low concentrations on cutaneous squamous cell carcinoma (cSCC) cells
3C), with double the number of cells undergoing early apoptosis (3.5 μM: 10.0% ± 1.8, 7 μM: 11.1% ± 2.3, 15 μM: 16.4% ± 0.7) with respect to those dying by late apoptosis or necrosis (3.5 μM: 19.5% ± 6.0, 7 μM: 21.2% ± 5.5, 15 μM: 36.3% ± 1.3)
Summary
Cis-diamminedichloroplatinum (II) (cisplatin or cisPt) is an alkylating neutral complex, widely used as a chemotherapeutic agent against a broad range of cancers, showing substantial therapeutic impact against most carcinoma-like tumors [1,2]. Cisplatin as a potential chemotherapeutic agent against skin cancer. Members of the Mistral beamline at ALBA synchrotron helped in the data collection and analysis, as well as in the preparation of the manuscript
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