Oligomer procyanidins from grape seeds induce a paraptosis-like programmed cell death in human glioblastoma U-87 cells.
BACKGROUND
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 glioblastoma cells induced by F2 and gained insight into the nature of the signaling pathways activated by F2 in glioblastoma cells.


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.


CONCLUSIONS
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.
Zhang
Feng-Jiao
FJ
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, PR China.
Yang
Jing-Yu
JY
Mou
Yan-Hua
YH
Sun
Bao-Shan
BS
Wang
Ji-Ming
JM
Wu
Chun-Fu
CF
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012639:Seeds; D027843:Vitis
D010936:Plant Extracts; D044945:Proanthocyanidins