Sensitizing mucoepidermoid carcinomas to chemotherapy by targeted disruption of cancer stem cells.
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.
Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA.|Department of Oral Pathology, School of Dentistry, University of Sao Paulo, SP, Brazil.
Douglas M
DM
Guimarães
Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA.
Luciana O
LO
Almeida
Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA.|Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Manoela D
MD
Martins
Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Kristy A
KA
Warner
Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas, Campinas, SP, Brazil.
Alan R S
AR
Silva
Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas, Campinas, SP, Brazil.
Pablo A
PA
Vargas
Department of Oral Pathology, School of Dentistry, University of Sao Paulo, SP, Brazil.
Fabio D
FD
Nunes
Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA.|Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Cristiane H
CH
Squarize
Department of Otolaryngology, Medical School, University of Michigan, Ann Arbor, MI, USA.|Department of Restorative Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Jacques E
JE
Nör
Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA.
Rogerio M
RM
Castilho
D000107:Acetylation; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D018277:Carcinoma, Mucoepidermoid / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D010641:Phenotype; D012468:Salivary Gland Neoplasms / Q000188:drug therapy / Q000473:pathology*; D012469:Salivary Glands / Q000473:pathology; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D002945:Cisplatin
cancer initiating cells; epigenetic; histone acetylation; histone modifications; salivary cancer