SapC-DOPS-induced lysosomal cell death synergizes with TMZ in glioblastoma

Academic Article

Abstract

  • SapC-DOPS is a novel nanotherapeutic that has been shown to target and induce cell death in a variety of cancers, including glioblastoma (GBM). GBM is a primary brain tumor known to frequently demonstrate resistance to apoptosis-inducing therapeutics. Here we explore the mode of action for SapC-DOPS in GBM, a treatment being developed by Bexion Pharmaceuticals for clinical testing in patients. SapC-DOPS treatment was observed to induce lysosomal dysfunction of GBM cells characterized by decreased glycosylation of LAMP1 and altered proteolytic processing of cathepsin D independent of apoptosis and autophagic cell death. We observed that SapC-DOPS induced lysosomal membrane permeability (LMP) as shown by LysoTracker Red and Acridine Orange staining along with an increase of sphingosine, a known inducer of LMP. Additionally, SapC-DOPS displayed strong synergistic interactions with the apoptosis-inducing agent TMZ. Collectively our data suggest that SapC-DOPS induces lysosomal cell death in GBM cells, providing a new approach for treating tumors resistant to traditional apoptosis-inducing agents.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Wojton J; Meisen WH; Jacob NK; Thorne AH; Hardcastle J; Denton N; Chu Z; Dmitrieva N; Marsh R; Van Meir EG
  • Start Page

  • 9703
  • End Page

  • 9709
  • Volume

  • 5
  • Issue

  • 20