Abstract A191: DHMEQ: A novel NF-kappaB inhibitor with good results in pediatric medulloblastoma cell lines

• Published in: Molecular cancer therapeutics 2013-11, Vol.12 (11_Supplement), p.A191-A191
• Main Authors: Ramos, Priscila Maria Manzini, Castro-Gamero, Angel Mauricio, Pezuk, Julia Alejandra, Scrideli, Carlos Alberto, Umezawa, Kazuo, Tone, Luiz Gonzaga
• Format: Article
• Language: English
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.TARG-13-A191

Medulloblastoma (MB) is the most common malignant central nervous system tumor of childhood representing 15-30% of pediatric brain tumors. The standard treatment involves surgery and chemotherapy and radiotherapy is used only for patients older than 3 years old. The risk of neurocognitive sequel, growth and endocrine systems leading the search for new therapeutic approaches. Great efforts have been made to improve treatments with high success rates and minimal toxicity, among them DHMEQ is a drug that has shown a low toxicity and high effectivity in blocking the NFkappaB, a key transcription factor that control the expression of a large number of genes related to cell proliferation, growth and apoptosis, showing antineoplasic effects in several cancer cell lines. There are no reports showing the effects of DHMEQ in MB. Cell proliferation, clonogenic capacity, wound healing assay, apoptosis (Annexin V), and combination with chemotherapeutic drugs (Cisplatin (CDDP), Temozolomide (TMZ) and Etoposide) or radiation were performed on three pediatric MB cell lines: UW402, UW473 e ONS76. Functional tests were performed using 0-20 µg/mL DHMEQ at 24, 48 and 72h. IC50 values of each drug and drug combination analyses were based in Chou-Talalay method, and simultaneous treatments of DHMEQ with CDDP (2:1 ratio), TMZ (1:200 ratio) or Etoposide (1:0,8 ratio) were performed for 48h or 72h. For gamma radiation clonogenic survival assays were used the doses of 2, 4 and 6 Gy. Statistical analysis was made by ANOVA and Pairwise Multiple Comparison de Holm-Sidak tests (SigmaStat 3.5). All experiments showed DHMEQ caused a decrease on cell proliferation, viability, migration ratio and clonogenic capacity, while increase apoptosis (P