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

Jeffrey Wojton, Walter Hans Meisen, Naduparambil K. Jacob, Amy Haseley Thorne, Jayson Hardcastle, Nicholas Denton, Zhengtao Chu, Nina Dmitrieva, Rachel Marsh, Erwin G. Van Meir, Chang Hyuk Kwon, Arnab Chakravarti, Xiaoyang Qi, Balveen Kaur

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)9703-9709
Number of pages7
Issue number20
StatePublished - 2014
Externally publishedYes


  • Glioblastoma
  • Lysosomal dysfunction
  • SapC-DOPS
  • Synergy
  • TMZ

ASJC Scopus subject areas

  • Oncology


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