Research Papers:

Sensitizing mucoepidermoid carcinomas to chemotherapy by targeted disruption of cancer stem cells

Douglas M. Guimarães, Luciana O. Almeida, Manoela D. Martins, Kristy A. Warner, Alan R. S. Silva, Pablo A. Vargas, Fabio D. Nunes, Cristiane H. Squarize, Jacques E. Nör _ and Rogerio M. Castilho

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Oncotarget. 2016; 7:42447-42460. https://doi.org/10.18632/oncotarget.9884

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Douglas M. Guimarães1,3,*, Luciana O. Almeida1,*, Manoela D. Martins1,4, Kristy A. Warner7, Alan R. S. Silva5, Pablo A. Vargas5, Fabio D. Nunes3, Cristiane H. Squarize1,2, Jacques E. Nör6,7, Rogerio M. Castilho1

1Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA

2Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA

3Department of Oral Pathology, School of Dentistry, University of Sao Paulo, SP, Brazil

4Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

5Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas, Campinas, SP, Brazil

6Department of Otolaryngology, Medical School, University of Michigan, Ann Arbor, MI, USA

7Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA

*These authors have contributed equally to this work

Correspondence to:

Rogerio M. Castilho, email: rcastilh@umich.edu

Keywords: salivary cancer, epigenetic, histone modifications, histone acetylation, cancer initiating cells

Received: January 04, 2016     Accepted: May 15, 2016     Published: June 7, 2016


Mucoepidermoid carcinoma (MEC) is the most common malignancy of salivary glands. The response of MEC to chemotherapy is unpredictable, and recent advances in cancer biology suggest the involvement of cancer stem cells (CSCs) in tumor progression and chemoresistance and radioresistance phenotype. We found that histone acetyltransferase inhibitors (HDACi) were capable of disrupting CSCs in MEC. Furthermore, administration of HDACi prior to Cisplatin (two-hit approach) disrupts CSCs and sensitizes tumor cells to Cisplatin. Our findings corroborate to emerging evidence that CSCs play a key role in tumor resistance to chemotherapy, and highlights a pharmacological two-hit approach that disrupts tumor resistance to conventional therapy.

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