RRC ID 56134
Author Peng F, Wang X, Shu M, Yang M, Wang L, Ouyang Z, Shen C, Hou X, Zhao B, Wang X, Zhang LW, Liu Y, Zhao S.
Title Raddeanin a Suppresses Glioblastoma Growth by Inducing ROS Generation and Subsequent JNK Activation to Promote Cell Apoptosis.
Journal Cell Physiol Biochem
Abstract BACKGROUND/AIMS:Raddeanin A (RA), an active pharmacological ingredient from Anemone raddeana Regel, plays an important role in tumor suppression. In this study, we assessed the potentially therapeutic effect of RA on glioblastoma and its underlying mechanisms.
METHODS:Cell viability was examined using the MTT assay. Invasive and migratory capacities were examined using Transwell and wound healing assays. Apoptosis was determined by Hoechst staining, flow cytometry, DCFH-fluorescent probe and immunohistochemical staining. Autophagy was detected by transmission electron microscopy and western blotting. A U251 glioma xenograft model was established to evaluate the effect of RA in vivo.
RESULTS:The data demonstrated that RA inhibited viability, and abrogated the invasive/migratory abilities of glioblastoma cells. In addition, RA induced apoptosis by reactive oxygen species (ROS)/ Jun N-terminal kinase (JNK) signaling in glioblastoma. Conversely, the antioxidant N-Acetyl-L-cysteine (NAC) and pan-caspase inhibitor z-VAD-fmk attenuated RA-induced apoptosis by scavenging ROS and inactivating caspase-3. Furthermore, the inhibition of autophagy by 3-MA exacerbated apoptosis through ROS generation and JNK phosphorylation. In vivo, RA exhibited a curative effect on U251-derived xenografts in nude mice.
CONCLUSIONS:The results of this study suggest that RA suppressed the growth of glioblastoma, thus serving as a promising and potential strategy for glioblastoma chemotherapy.
Volume 47(3)
Pages 1108-1121
Published 2018-5-25
DOI 10.1159/000490187
PII 000490187
PMID 29843152
MeSH Apoptosis / drug effects* Cell Line, Tumor Enzyme Activation / drug effects Glioblastoma / drug therapy Glioblastoma / metabolism* Glioblastoma / pathology Humans MAP Kinase Kinase 4 / metabolism* Neoplasm Proteins / metabolism* Reactive Oxygen Species / metabolism* Saponins / pharmacology*
IF 5.5
Times Cited 12
Human and Animal Cells T98G(RCB1954)