Prodigiosin stimulates endoplasmic reticulum stress and induces autophagic cell death in glioblastoma cells.

Abstract

Prodigiosin, a secondary metabolite isolated from marine Vibrio sp., has antimicrobial and anticancer properties. This study investigated the cell death mechanism of prodigiosin in glioblastoma. Glioblastoma multiforme (GBM) is an aggressive primary cancer of the central nervous system. Despite treatment, or standard therapy, the median survival of glioblastoma patients is about 14.6 month. The results of the present study clearly showed that prodigiosin significantly reduced the cell viability and neurosphere formation ability of U87MG and GBM8401 human glioblastoma cell lines. Moreover, prodigiosin with fluorescence signals was detected in the endoplasmic reticulum and found to induce excessive levels of autophagy. These findings were confirmed by observation of LC3 puncta formation and acridine orange staining. Furthermore, prodigiosin caused cell death by activating the JNK pathway and decreasing the AKT/mTOR pathway in glioblastoma cells. Moreover, we found that the autophagy inhibitor 3-methyladenine reversed prodigiosin induced autophagic cell death. These findings of this study suggest that prodigiosin induces autophagic cell death and apoptosis in glioblastoma cells.

• Authors: Shu-Yu Cheng, Nan-Fu Chen, Hsiao-Mei Kuo, San-Nan Yang, Chun-Sung Sung, Ping-Jyun Sung, Zhi-Hong Wen, Wu-Fu Chen
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 23 Issue 5-6 Pg. 314-328 (06 2018) ISSN: 1573-675X [Electronic] Netherlands
• PMID: 29721785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Calnexin
• Proto-Oncogene Proteins c-akt
• Caspase 3
• Prodigiosin

Topics

• Antineoplastic Agents
• Autophagy (drug effects)
• Calnexin (metabolism)
• Caspase 3 (metabolism)
• Drug Screening Assays, Antitumor
• Endoplasmic Reticulum Stress (drug effects)
• Glioblastoma (drug therapy)
• Humans
• MAP Kinase Signaling System (drug effects)
• Prodigiosin (isolation & purification, pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Tumor Cells, Cultured