Targeting Notch Signaling and Autophagy Increases Cytotoxicity in Glioblastoma Neurospheres.

ABSTRACT: Glioblastomas are highly aggressive tumors that contain treatment resistant stem-like cells. Therapies targeting developmental pathways such as Notch eliminate many neoplastic glioma cells, including those with stem cell features, but their efficacy can be limited by various mechanisms. One potential avenue for chemotherapeutic resistance is the induction of autophagy, but little is known how it might modulate the response to Notch inhibitors. We used the γ-secretase inhibitor MRK003 to block Notch pathway activity in glioblastoma neurospheres and assessed its effects on autophagy. A dramatic, several fold increase of LC3B-II/LC3B-I autophagy marker was noted on western blots, along with the emergence of punctate LC3B immunostaining in cultured cells. By combining the late stage autophagy

SUBMITTER: Natsumeda M 

PROVIDER: S-EPMC8029219 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature