Sensitizing mucoepidermoid carcinomas to chemotherapy by targeted disruption of cancer stem cells
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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
Rogerio M. Castilho, email: email@example.com
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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