5-Aza-CdR Promotes Partial MGMT Demethylation and Modifies Expression of Different Genes in OSCC

Publication date: Available online 11 January 2019

Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology

Author(s): Guilherme C.L.S. do Amaral, Aline C. Planello, Gabriell Borgatto, Dieila Giomo de Lima, Gustavo N. Guimarães, Marcelo Rocha Marques, Ana Paula de Souza

ABSTRACT

Objective

Treatment strategies for Oral Squamous Cell Carcinoma (OSCC) vary based on the stage of diagnosis. Surgery and radiotherapy are options for localized lesions for stage I patients, while chemotherapy is the main treatment for metastatic OSCC. However, aggressive tumors can relapse, causing frequently the death of the patient. In an attempt to address this, novel treatment protocols using epigenetic drugs that alter the epigenetic profile have emerged as an alternative to control tumor growth and metastasis. Therefore, our objective in this study was to investigate the effect of demethylating drug 5-aza-CdR at the concentrations of 0.3 μM and 2 μM in SCC9 cells.

Study Design

SCC9 cells were treated with 5-Aza-CdR at the concentrations of 0.3 μM and 2 μM for 24 h and 48 h. DNA methylation of MGMT, BRCA1, APC, c-MYC and hTERT genes were investigated using Methylation Specific-High Resolution Melting technique. RT-PCR and qPCR were performed to analyze genes expression.

Results

5-Aza-CdR promoted demethylation of MGMT gene and modified the transcription of all analyzed genes. Curiously, 5-aza-CdR at the concentration of 0.3 μM was more efficient than 2 μM in SCC9 cells.

Conclusion

We observed 5-aza-CdR led to MGMT demethylation, upregulated transcription of three important tumor suppressor genes and promoted downregulation of c-Myc.

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