PI3K/mTOR Inhibitor Induces Context-Dependent Apoptosis and Methuosis in Cancer Cells.

ABSTRACT: Background/Objectives: Targeting the PI3K/mTOR pathway is a promising strategy in cancer therapy, but its efficacy is often limited by apoptosis resistance. This study investigates the dual PI3K/mTOR inhibitor YYN-37, exploring its capacity to induce context-dependent cell death, particularly the non-apoptotic process of methuosis. Methods: We examined the effects of YYN-37 on HCT-116 and SJSA-1 cancer cell lines using cell viability assays, Western blot, and fluorescent tracers. Cell death mechanisms were probed with pathway-specific inhibitors. The role of VPS34 was assessed through kinase activity assays, siRNA-mediated knockdown, and rescue experiments with the agonist leucine. Proteomic profiling and an in vivo SJSA-1 xenograft model in BALB/c nude mice were utilized to

SUBMITTER: Hua X 

PROVIDER: S-EPMC12736009 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature