Targeting c-IAP1, c-IAP2, and Bcl-2 Eliminates Senescent Glioblastoma Cells Following Temozolomide Treatment.

ABSTRACT: Therapy of malignant glioma depends on the induction of O⁶-methylguanine by the methylating agent temozolomide (TMZ). However, following TMZ exposure, most glioma cells evade apoptosis and become senescent and are thereby protected against further anticancer therapy. This protection is thought to be dependent on the senescent cell anti-apoptotic pathway (SCAP). Here we analyzed the factors involved in the SCAP upon exposure to TMZ in glioblastoma cell lines (LN-229, A172, U87MG) and examined whether inhibition of these factors could enhance TMZ-based toxicity by targeting senescent cells. We observed that following TMZ treatment, c-IAP2 and Bcl-2 were upregulated. Inhibition of these SCAP factors using non-toxic concentrations of the small molecule inhibitors, BV6 and venetoclax

SUBMITTER: Schwarzenbach C 

PROVIDER: S-EPMC8306656 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature