Evaluation of antineoplastic effects of Zebularina on medulloblastoma cell lines

Abstract

Medulloblastoma is a central nervous system cancer, which arises in the cerebellum. Its origin is embryonic and is considered highly invasive. It is the most common solid tumor in pediatric patients and its occurrence is more common in 5-7 year-old children. Corresponds to approximately 20% of all pediatric intracranial tumors. The most common treatment is surgery and chemotherapy, and radiotherapy is applied only to children over 3 years because of its side effects in the central nervous system. Several factors contribute to the development and progression of medulloblastoma. Among these, there are changes in signaling pathways such as Hedgehog, Notch and WNT, and epigenetic changes, such as acetylation and methylation of DNA. Such changes undertakes basic cell functions such as controlling apoptosis, cell proliferation, angiogenesis and metastasis. Despite the growing understanding of molecular mechanisms of MB, there are no therapies that significantly increase the survival of patients avoiding late side effects. Recently, epigenetic drugs as DNA methyltransferases inhibitors (iDNMTs) has shown promising results and anticancer effects both in hematologic and solid tumors. Zebularina is an iDNMTs that causes DNA demethylation. This agent has proved to be an antitumor drug with low toxicity, with adjuvant activity in anti-cancer chemotherapy in chemo-resistant tumors and is a great option for drug combination. Several studies have shown the anticancer effects of Zebularina in different types of cancer, however, there are no studies that report these effects in medulloblastoma cell lines.