Are There Thresholds in Glioblastoma Cell Death Responses Triggered by Temozolomide?

ABSTRACT: Temozolomide (TMZ) is an alkylating agent used in the treatment of high-grade malignant glioma, notably glioblastoma multiforme, the most aggressive form of brain cancer. The drug induces a dozen DNA methylation adducts, including O⁶-methylguanine (O⁶MeG), which is the most toxic primary DNA lesion as it causes the formation of DNA double-strand breaks (DSBs) that trigger apoptosis. In p53 wild-type cells, TMZ activates p-p53ser15 and p-p53ser46, which have opposing dual functions regulating survival and death, respectively. Since the use of TMZ in a therapeutic setting is limited because of its side effects, the question arises as to the existence of threshold doses that activate the death pathway and start apoptosis. To determine whether there is a threshold for the TMZ-ind

SUBMITTER: He Y 

PROVIDER: S-EPMC6480213 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature