Evaluation of acetylation and methylation in oral rinse of patients with head and neck cancer history exposed to valproic acid

Author(s)

Gama, Ricardo Ribeiro ^{[1, 2]} ; Rebolho Batista Arantes, Lidia Maria ^[3] ; Sorroche, Bruna Pereira ^[3] ; De Marchi, Pedro ^{[4, 5]} ; Melendez, Matias Eliseo ^[3] ; Carvalho, Raiany Santos ^[6] ; de Lima, Marcos Alves ^[7] ; Vettore, Andre Luiz ^[8] ; Carvalho, Andre Lopes ^{[3, 1, 9]}

Affiliation

^[1] Barretos Canc Hosp, Head & Neck Surg Dept, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos, SP - Brazil

^[2] Sao Paulo Fed Univ, Postgrad Program, Sao Paulo, SP - Brazil

^[3] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos, SP - Brazil

^[4] Oncoclinicas, Rio De Janeiro, RJ - Brazil

^[5] Barretos Canc Hosp, Clin Oncol Dept, Barretos, SP - Brazil

^[6] Barretos Canc Hosp, Researcher Support Ctr, Teaching & Res Inst, Barretos, SP - Brazil

^[7] Barretos Canc Hosp, Biostat Ctr, Teaching & Res Inst, Barretos, SP - Brazil

^[8] Sao Paulo Fed Univ, Canc Mol Biol Lab, Diadema, SP - Brazil

^[9] Int Agcy Res Canc IARC, Lyon - France

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 AUG 12 2021.
• Web of Science Citations: 0

Abstract

Evaluate the biological action of valproic acid in the acetylation of histones and in the methylation of tumor suppressor genes via oral rinse in patients with a previous history of head and neck squamous cell carcinoma (HNSCC). Forty-two active or former smokers were included in this randomized, double-blind, placebo-controlled trial. Oral rinse samples were collected prior to treatment with valproic acid or placebo and after 90 days of treatment. The methylation status of five tumor suppressor genes and histone acetylation were evaluated by pyrosequencing and ELISA techniques, respectively. Differences between the 90-day and baseline oral rinse acetylation and methylation results were analyzed by comparing groups. Thirty-four patients were considered for analysis. The mean percentage adherence in the valproic and placebo groups was 93.4 and 93.0, respectively (p = 0.718). There was no statistically significant difference between groups when comparing the medians of the histone acetylation ratio and the methylation ratio for most of the studied genes. A significant reduction in the DCC methylation pattern was observed in the valproic group (p = 0.023). The use of valproic acid was safe and accompanied by good therapeutic adherence. DCC methylation was lower in the valproic acid group than in the placebo group. (AU)

• FAPESP's process: 15/12990-0 - Methylation as a response modulation mechanism to EGFR inhibitors in Head and Neck Carcinoma
• Grantee: Lidia Maria Rebolho Batista Arantes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral