Multiparametric analysis of the effectiveness of cisplatin on cutaneous squamous carcinoma cells using two different types of adjuvants

PLoS One. 2020 Mar 6;15(3):e0230022. doi: 10.1371/journal.pone.0230022. eCollection 2020.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Size / drug effects
  • Chelating Agents / chemistry
  • Cisplatin / chemistry*
  • Cisplatin / pharmacology
  • Drug Carriers / chemistry*
  • Glycine / analogs & derivatives
  • Glycine / chemistry
  • Glycine / toxicity
  • Gold / chemistry
  • Humans
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / toxicity
  • Microscopy, Electron, Transmission
  • Signal Transduction / drug effects
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Chelating Agents
  • Drug Carriers
  • Gold
  • Cisplatin
  • Glycine
  • tricine

Grants and funding

1) S.G., M.A., M.S. received the funding of the Asociación Española Contra el Cáncer (Federació de Barcelona), and the Institut d'Investigació i Innovació Parc Taulí (I3PT). https://www.aecc.es/es/sobre-nosotros/donde-estamos/sede-barcelonahttp://www.tauli.cat/i3pt/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 2) S.G., E.S., F.M.-T., J.M.-E., A.J.P.-B., J.J.C., C.K.-L., M.A., M.S. received the funding of synchrotron ALBA to perform part of this work in the Mistral beamline of this light source. Members of the Mistral beamline at ALBA synchrotron helped in the data collection and analysis, as well as in the preparation of the manuscript.