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Oncotarget. 2016 Jul 5;7(27):42447-42460. doi: 10.18632/oncotarget.9884.

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

Author information

1
Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA.
2
Department of Oral Pathology, School of Dentistry, University of Sao Paulo, SP, Brazil.
3
Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
4
Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
5
Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas, Campinas, SP, Brazil.
6
Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
7
Department of Otolaryngology, Medical School, University of Michigan, Ann Arbor, MI, USA.

Abstract

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.

KEYWORDS:

cancer initiating cells; epigenetic; histone acetylation; histone modifications; salivary cancer

PMID:
27285758
PMCID:
PMC5173147
DOI:
10.18632/oncotarget.9884
[Indexed for MEDLINE]
Free PMC Article

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