TY - JOUR
T1 - Cytotoxic effects of 5-azacytidine on primary tumour cells and cancer stem cells from oral squamous cell carcinoma
T2 - An in vitro ftirm analysis
AU - Notarstefano, Valentina
AU - Belloni, Alessia
AU - Sabbatini, Simona
AU - Pro, Chiara
AU - Orilisi, Giulia
AU - Monterubbianesi, Riccardo
AU - Tosco, Vincenzo
AU - Byrne, Hugh J.
AU - Vaccari, Lisa
AU - Giorgini, Elisabetta
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - 5-azacytidine
KW - DNA methylation
KW - Fourier Transform InfraRed Microscospectroscopy
KW - OSCC cancer stem cells
KW - OSCC primary cells
KW - Oral squamous cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85115042371&partnerID=8YFLogxK
U2 - 10.3390/cells10082127
DO - 10.3390/cells10082127
M3 - Article
C2 - 34440896
AN - SCOPUS:85115042371
SN - 2073-4409
VL - 10
JO - Cells
JF - Cells
IS - 8
M1 - 2127
ER -