Oligomer procyanidins from grape seeds induce a paraptosis-like programmed cell death in human glioblastoma U-87 cells

Abstract

Context: We recently reported that F2, an oligomer procyanidin fraction isolated from grape seeds, triggered an original form of cell death in U-87 human glioblastoma cells with a phenotype resembling morphological characteristics of paraptosis. However, the specific death mode induced by F2 and the mechanism of its action have not been assessed so far.

Objective: In the present work, we therefore further investigated the death mode of human glioblastma cells induced by F2 and gained insight into the nature of the signaling pathways activated by F2 in glioblastoma cells.

Materials and methods: Cell viability assay using MTT, (AO/EB) double staining, Western blot analysis, and Ca²⁺ assay using fura-2.

Results: Morphology studies revealed extensive cytoplasmic vacuolization in dying cells and no apoptotic body formation, membrane bleb formation, or nuclear fragmentation, though some was accompanied by MAPK activation and new protein synthesis, and was independent of caspase activation. Moreover, we demonstrated the involvement of calcium mobilization in F2-induced U-87 cell signaling.

Discussion and conclusion: Altogether we showed that F2 induced a kind of cell death resembling paraptosis in U-87 cells. The current report complements previous studies on the characterization of F2-induced U-87 cell death, enhances our understanding of the action mechanism of F2 on glioma, and helps in the development of novel antitumor therapeutics.

Keywords::

• Calcium mobilization
• glioma
• grape seed extract
• MAPKs
• oligomer procyanidins
• paraptosis