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Cell Physiol Biochem. 2018;47(3):1108-1121. doi: 10.1159/000490187. Epub 2018 May 25.

Raddeanin a Suppresses Glioblastoma Growth by Inducing ROS Generation and Subsequent JNK Activation to Promote Cell Apoptosis.

Peng F1,2, Wang X1,2, Shu M1,2, Yang M1,2, Wang L1,2, Ouyang Z1,2, Shen C1,2, Hou X1,2, Zhao B1,2, Wang X1,2, Zhang LW3, Liu Y1,2,4, Zhao S1,2.

Author information

1
Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China.
2
Institute of Brain Science, Harbin Medical University, Harbin, China.
3
Shanghai Medical College, Fudan University, Shanghai, China.
4
Department of Neurosurgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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.

KEYWORDS:

Apoptosis; Autophagy; Glioblastoma; ROS/JNK signaling pathway; Raddeanin A

PMID:
29843152
DOI:
10.1159/000490187
[Indexed for MEDLINE]
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