Lys05 induces lysosomal membrane permeabilization and increases radiosensitivity in glioblastoma

• Published in: Journal of cellular biochemistry 2020-02, Vol.121 (2), p.2027-2037
• Main Authors: Zhou, Wei, Guo, Yulian, Zhang, Xin, Jiang, Zheng
• Format: Article
• Language: English
• Subjects: Aminoquinolines - pharmacology; Anticancer properties; Antitumor activity; Apoptosis; Autophagy; Brain cancer; Brain tumors; Cell death; Cell Membrane Permeability; Cell Proliferation; Cell viability; Cytosol; Depolarization; Gamma Rays; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - pathology; Glioblastoma - radiotherapy; Glioma cells; Humans; Lys05; lysosomal membrane permeabilization; Lysosomes; Lysosomes - drug effects; Lysosomes - metabolism; Membranes; Mitochondria; Phagocytosis; Polyamines - pharmacology; Radiation Tolerance - drug effects; Radiation-Sensitizing Agents - pharmacology; Radiosensitivity; TFEB; Tumor Cells, Cultured
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.29437

Glioblastoma (GBM) is one of the most malignant primary brain tumors and its prognosis is very poor. Lysosome‐dependent cell death is mainly caused by lysosomal membrane permeabilization (LMP), a process in which the lysosome loses its membrane integrity and lysosomal contents are released into the cytosol. Lysosomotropic agent, a kind of compound that selectively accumulates in the lysosomes, is one of the most important inducers of LMP. As a newly‐synthetic lysosomotropic agent, Lys05 showed efficient autophagy inhibiting and antitumor effect. But its mechanisms are not well illustrated. Here, we studied whether Lys05 has antiglioma activity. We found that Lys05 decreased cell viability and reduced cell growth of glioma U251 and LN229 cells. After Lys05 treatment, autophagic flux is inhibited and lysosome function is impaired. We also found that Lys05 caused LMP and mitochondrial depolarization. Finally, Lys05 increased radiosensitivity in an LMP‐dependent manner. For the first time, our findings indicate that LMP contributes to radiosensitivity in GBM cells. Therefore, LMP inducer, Lys05 might be a promising compound in the treatment of GBM cells. Lys05 showed efficient antitumor effect on glioblastoma cells. Lys05‐induced lysosomal membrane permeabilization (LMP) and increased radiosensitivity. LMP increases radiosensitivity.