Cephaeline is an inductor of histone H3 acetylation and inhibitor of mucoepidermoid carcinoma cancer stem cells

Author(s):Show less -

Silva, Luan Cesar ^[1] ; Borgato, Gabriell Bonifacio ^[1] ; Wagner, Vivian Petersen ^[2] ; Martins, Manoela Domingues ^{[1, 3]} ; Rocha, Guilherme Zweig ^[1] ; Lopes, Marcio Ajudarte ^[1] ; Santos-Silva, Alan Roger ^[1] ; de Castro Junior, Gilberto ^[4] ; Kowalski, Luiz Paulo ^[5] ; Nor, Jacques E. ^[6] ; Squarize, Cristiane H. ^[7] ; Castilho, Rogerio Moraes ^[7] ; Vargas, Pablo Agustin ^[1]

Affiliation

^[1] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Oral Diag, Sao Paulo - Brazil

^[2] Univ Sheffield, Acad Unit Oral & Maxillofacial Med & Pathol, Dept Clin Dent, Sheffield, S Yorkshire - England

^[3] Univ Fed Rio Grande do Sul, Sch Dent, Dept Oral Pathol, Porto Alegre, RS - Brazil

^[4] Univ Sao Paulo, Sao Paulo State Canc Inst ICESP, Clin Oncol Serv, Sch Med, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Med, AC Camargo Canc Ctr, Head & Neck Surg & Otorhinolaryngol Dept, Dept Hea, Sao Paulo - Brazil

^[6] Univ Michigan, Sch Dent, Dept Cariol, Restorat Sci, Endodont, Ann Arbor, MI 48109 - USA

^[7] Univ Michigan, Sch Dent, Lab Epithelial Biol, Dept Periodont & Oral Med, Ann Arbor, MI 48109 - USA

• Document type: Journal article
• Source: JOURNAL OF ORAL PATHOLOGY & MEDICINE; OCT 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 19/06597-5 - Disrupting tumor resistance through therapy targeting depletion of cancer stem cells in Salivary Mucoepidermoid Carcinomas
• Grantee: Luan César da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/05710-4 - Disrupting tumor resistance through therapy targeting depletion of cancer stem cells in head and neck cancer
• Grantee: Pablo Agustin Vargas
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/21785-4 - Association of BDNF/TRKB signaling pathway with tumor agressiveness and cancer stem cell profile of malignant salivary gland tumors
• Grantee: Vivian Petersen Wagner
• Support Opportunities: Scholarships in Brazil - Post-Doctoral