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.

Malvidin induces hepatic stellate cell apoptosis via the endoplasmic reticulum stress pathway and mitochondrial pathway

“…Endoplasmic reticulum stress (ERS) is important for the interplay of apoptosis in many cells (Cheng et al., 2018). Excessive ERS can induce cell apoptosis by activating critical mediators, caspase‐12 and C/EBP homologous protein (CHOP; Görlach, Klappa, & Kietzmann, 2006).…”

<p>Brevilin A Inhibits STAT3 Signaling and Induces ROS-Dependent Apoptosis, Mitochondrial Stress and Endoplasmic Reticulum Stress in MCF-7 Breast Cancer Cells</p>

“…Binding immunoglobulin protein BiP/ GRP78 is activated during ER stress to degrade misfolded proteins. 27 Significant increase in BiP/GRP78 expression was observed in Brv-A treated cells. We also observed significant increase in expression of activating transcription factor 4 (ATF4) and pro-death transcriptional regulator, C/EBP homologous protein (CHOP) in Brv-A treated cells which are hallmarks of ER stress-induced apoptosis.…”

Programmed death, cells on the last train to glory

“…IL6/GP130 inhibitors were found to increase the activity of 5-fluorouracil in colon cancer, suggesting a promising strategy for future therapy [11]. An antimicrobial compound with anti-cancer activity, prodigiosin, was found to inhibit glioblastoma cells, through inhibition of the JNK and the AKT/mTOR pathways, while inducing an excessive level of autophagy [12]. This study suggests unexpected opportunities for this compound.…”