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Cephaeline is an inductor of histone H3 acetylation and inhibitor of mucoepidermoid carcinoma cancer stem cells.
Silva, Luan César; Borgato, Gabriell Bonifácio; Wagner, Vivian Petersen; Martins, Manoela Domingues; Rocha, Guilherme Zweig; Lopes, Márcio Ajudarte; Santos-Silva, Alan Roger; de Castro Júnior, Gilberto; Kowalski, Luiz Paulo; Nor, Jacques E; Squarize, Cristiane H; Castilho, Rogerio Moraes; Vargas, Pablo Agustin.
Affiliation
  • Silva LC; Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
  • Borgato GB; Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
  • Wagner VP; Academic Unit of Oral and Maxillofacial Medicine and Pathology, Department of Clinical Dentistry, University of Sheffield, Sheffield, UK.
  • Martins MD; Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
  • Rocha GZ; Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
  • Lopes MA; Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
  • Santos-Silva AR; Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
  • de Castro Júnior G; Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
  • Kowalski LP; Clinical Oncology Service, São Paulo State Cancer Institute (ICESP), School of Medicine of the University of São Paulo, São Paulo, Brazil.
  • Nor JE; Department of Head and Neck Surgery, Faculty of Medicine, Head and Neck Surgery and Otorhinolaryngology Department, A C Camargo Cancer Center, Universidade de São Paulo, São Paulo, Brazil.
  • Squarize CH; Department of Cariology, Restorative Sciences, Endodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA.
  • Castilho RM; Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.
  • Vargas PA; Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.
J Oral Pathol Med ; 51(6): 553-562, 2022 Jul.
Article in En | MEDLINE | ID: mdl-34661317
ABSTRACT

AIM:

To evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas (MEC) of the salivary glands. MATERIAL AND

METHODS:

UM-HMC-1, UM-HMC-2, and UM-HMC-3A MEC cell lines were used to establish the effects of Cephaeline over tumor viability determined by MTT assay. In vitro wound healing scratch assays were performed to address cellular migration while immunofluorescence staining for histone H3 lysine 9 (H3k9ac) was used to identify the acetylation status of tumor cells upon Cephaeline administration. The presence of cancer stem cells was evaluated by the identification of ALDH enzymatic activity by flow cytometry and through functional assays using in vitro tumorsphere formation.

RESULTS:

A single administration of Cephaeline resulted in reduced viability of MEC cells along with the halt on tumor growth and cellular migration potential. Administration of Cephaeline resulted in chromatin histone acetylation as judged by the increased levels of H3K9ac and disruption of tumorspheres formation. Interestingly, ALDH levels were increased in UM-HMC-1 and UM-HMC-3A cell lines, while UM-HMC-2 showed a reduced enzymatic activity.

CONCLUSION:

Cephaeline has shown anti-cancer properties in all MEC cell lines tested by regulating tumor cells' viability, migration, proliferation, and disrupting the ability of cancer cells to generate tumorspheres.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Mucoepidermoid Limits: Humans Language: En Journal: J Oral Pathol Med Journal subject: ODONTOLOGIA / PATOLOGIA Year: 2022 Type: Article Affiliation country: Brazil
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Mucoepidermoid Limits: Humans Language: En Journal: J Oral Pathol Med Journal subject: ODONTOLOGIA / PATOLOGIA Year: 2022 Type: Article Affiliation country: Brazil