Format

Send to

Choose Destination
Front Cell Neurosci. 2017 Sep 29;11:310. doi: 10.3389/fncel.2017.00310. eCollection 2017.

Dihydroartemisinin Exerts Anti-Tumor Activity by Inducing Mitochondrion and Endoplasmic Reticulum Apoptosis and Autophagic Cell Death in Human Glioblastoma Cells.

Qu C1,2,3, Ma J4,5,6, Liu X1,2,3, Xue Y4,5,6, Zheng J1,2,3, Liu L4,5,6, Liu J1,2,3, Li Z1,2,3, Zhang L1,2,3, Liu Y1,2,3.

Author information

1
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
2
Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, China.
3
Liaoning Key Laboratory of Neuro-Oncology, Shenyang, China.
4
Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, China.
5
Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang, China.
6
Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang, China.

Abstract

Glioblastoma (GBM) is the most advanced and aggressive form of gliomas. Dihydroartemisinin (DHA) has been shown to exhibit anti-tumor activity in various cancer cells. However, the effect and molecular mechanisms underlying its anti-tumor activity in human GBM cells remain to be elucidated. Our results proved that DHA treatment significantly reduced cell viability in a dose- and time-dependent manner by CCK-8 assay. Further investigation identified that the cell viability was rescued by pretreatment either with Z-VAD-FMK, 3-methyladenine (3-MA) or in combination. Moreover, DHA induced apoptosis of GBM cells through mitochondrial membrane depolarization, release of cytochrome c and activation of caspases-9. Enhanced expression of GRP78, CHOP and eIF2α and activation of caspase 12 were additionally confirmed that endoplasmic reticulum (ER) stress pathway of apoptosis was involved in the cytotoxicity of DHA. DHA-treated GBM cells exhibited the morphological and biochemical changes typical of autophagy. Co-treatment with chloroquine (CQ) significantly induced the above effects. Furthermore, ER stress and mitochondrial dysfunction were involved in the DHA-induced autophagy. Further study revealed that accumulation of reactive oxygen species (ROS) was attributed to the DHA induction of apoptosis and autophagy. The illustration of these molecular mechanisms will present a novel insight for the treatment of human GBM.

KEYWORDS:

apoptosis; autophagy; dihydroartemisinin; endoplasmic reticulum; glioblastoma; mitochondrion; reactive oxygen species

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center