Cytotoxic effects of 5-azacytidine on primary tumour cells and cancer stem cells from oral squamous cell carcinoma: An in vitro ftirm analysis

Valentina Notarstefano, Alessia Belloni, Simona Sabbatini, Chiara Pro, Giulia Orilisi, Riccardo Monterubbianesi, Vincenzo Tosco, Hugh J. Byrne, Lisa Vaccari, Elisabetta Giorgini

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

In the present study, the cytotoxic effects of 5-azacytidine on primary Oral Squamous Cell Carcinoma cells (OSCCs) from human biopsies, and on Cancer Stem Cells (CSCs) from the same samples, were investigated by an in vitro Fourier Transform InfraRed Microscospectroscopy (FTIRM) approach coupled with multivariate analysis. OSCC is an aggressive tumoral lesion of the epithelium, accounting for ~90% of all oral cancers. It is usually diagnosed in advanced stages, and this causes a poor prognosis with low success rates of surgical, as well as radiation and chemotherapy treatments. OSCC is frequently characterised by recurrence after chemotherapy and by the development of a refractoriness to some employed drugs, which is probably ascribable to the presence of CSCs niches, responsible for cancer growth, chemoresistance and metastasis. The spectral information from FTIRM was correlated with the outcomes of cytotoxicity tests and image-based cytometry, and specific spectral signatures attributable to 5-azacytidine treatment were identified, allowing us to hypothesise the demethylation of DNA and, hence, an increase in the transcriptional activity, together with a conformational transition of DNA, and a triggering of cell death by an apoptosis mechanism. Moreover, a different mechanism of action between OSSC and CSC cells was highlighted, probably due to possible differences between OSCCs and CSCs response.

Original languageEnglish
Article number2127
JournalCells
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 2021

Keywords

  • 5-azacytidine
  • DNA methylation
  • Fourier Transform InfraRed Microscospectroscopy
  • OSCC cancer stem cells
  • OSCC primary cells
  • Oral squamous cell carcinoma

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