Valproic acid suppresses growth and enhances cisplatin cytotoxicity to larynx cancer cells.

Larynx cancer is the most common head and neck neoplasia in developed nations. The treatment of advanced larynx cancer include chemotherapy, often using cisplatin. The limitations of many antineoplastic drugs are their low delivery into respiratory tissues, thus the need of higher doses which results in severe side effects, and the development of drug resistance by cancer cells. Therefore the need of drugs and drug combinations that potentiates each other, increasing safety by reducing doses and act on several pathways at the same time, acting more specifically on cancer cells. Histone deacetylase inhibitors are a promising new class of anticancer agents. Among them valproic acid  is a well-established drug in psychiatry with a potential use in cancer treatment. Here we study the mechanisms of action of valproic acid on larynx cancer cells. Valproic acid treatment resulted in reduced proliferation and migration, increase in apoptosis, and cell cycle arrest in larynx cancer cells tested in our study. Valproic acid treatment induced the hyperacetylation of histone 3 K18 (H3 K18ac), resulting in de novo expression of CDKN1Aand simultaneously repressing of CCND1, thus affecting cell cycle progression. Moreover, valproic acid significantly potentiates the antineoplastic activity of cisplatin on larynx cancer cells, at low doses by increasing apoptosis, cell cycle arrest and reduced migration. Overall, our results suggest that valproic acid can potentially be used as a thera...
Source: Head and Neck Oncology - Category: Cancer & Oncology Source Type: research