Danthron induced apoptosis through mitochondria- and caspase-3-dependent pathways in human brain glioblastoma multiforms GBM 8401 cells.
Danthron (1,8-dihydroxyanthraquinone), is one of component from Rheum palmatum L. (Polygonaceae), has been shown several biological activities but did not show to induce apoptosis in human brain tumor cells. The aim of this study is to investigate the mechanisms by danthron for the induction of apoptotic potential on human brain glioblastoma multiforms GBM 8401 cell line. Danthron showed a marked concentration- and time-dependent inhibition of GBM 8401 cell viability and induced apoptosis in a dose-and time-dependent manner. There was an attenuation of mitochondrial membrane potential (DeltaPsi(m)) with the alterations of Bcl-2/Bax protein ratio in GBM 8401 cells, indicating the participation of a mitochondria-related mechanism. Pretreatment of a caspase-8 inhibitor (Z-IETD-FMK), caspase-9 inhibitor (Z-LEHD-FMK) and caspase-3 inhibitor (Z-DEVE-FMK) significantly increased the viable of GBM 8401 cells implied that the participations of caspases. Western blotting analysis also showed the activation of initiator caspase-8 and caspase-9, and executor caspase-3 in GBM 8401 cells. Meanwhile, danthron also promoted the generation of reactive oxygen species (ROS) and cytosolic Ca(2+) in GBM 8401 cells. Taken together, our data showed that danthron induced apoptosis in GBM 8401 cells through mitochondria-related and caspase-related pathways, and it may be further evaluated as a chemotherapeutic agent for human brain cancer.
Lu
Hsu-Feng
HF
Department of Clinical Pathology, Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan.
Wang
Hai-Lung
HL
Chuang
Ying-Ying
YY
Tang
Yih-Jing
YJ
Yang
Jai-Sing
JS
Ma
Yi-Shih
YS
Chiang
Jo-Hua
JH
Lu
Chi-Cheng
CC
Yang
Jiun-Long
JL
Lai
Tung-Yuan
TY
Wu
Chih-Chung
CC
Chung
Jing-Gung
JG
D000880:Anthraquinones / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000502:physiology*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D007211:Indoles; D008928:Mitochondria / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
D000880:Anthraquinones; D005456:Fluorescent Dyes; D007211:Indoles; D017382:Reactive Oxygen Species; C007293:DAPI; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D002118:Calcium; C004315:danthron