SapC-DOPS-induced Lysosomal Cell Death Synergizes with TMZ in Glioblastoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2014 Sep 12

PMID 25210852

Citations 20

Authors

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

Affiliations

Soon will be listed here.

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.

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