Inhibition of glioblastoma growth and angiogenesis by gambogic acid: an in vitro and in vivo study.
Gambogic acid (GA) is the major active ingredient of gamboge, a brownish to orange resin exuded from Garcinia hanburryi tree in Southeast Asia. The present study aims to demonstrate that gambogic acid (GA) has potent anticancer activity for glioblastoma by in vitro and in vivo study. Rat brain microvascular endothelial cells (rBMEC) were used as an in vitro model of the blood-brain barrier (BBB). To reveal an involvement of the intrinsic mitochondrial pathway of apoptosis, the mitochondrial membrane potential and the western blot evaluation of Bax, Bcl-2, Caspase-3, caspase-9 and cytochrome c released from mitochondria were performed. Angiogenesis was detected by CD31 immunochemical study. The results showed that the uptake of GA by rBMEC was time-dependent, which indicated that it could pass BBB and represent a possible new target in glioma therapy. GA could cause apoptosis of rat C6 glioma cells in vitro in a concentration-dependent manner by triggering the intrinsic mitochondrial pathway of apoptosis. In vivo study also revealed that i.v. injection of GA once a day for two weeks could significantly reduce tumor volumes by antiangiogenesis and apoptotic induction of glioma cells. Collectively, the current data indicated that GA may be of potential use in treatment of glioblastoma by apoptotic induction and antiangiogenic effects.
Qiang
Lei
L
Department of Physiology, Jiangsu Key Laboratory of Carcinogenesis and intervention, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Yang
Yong
Y
You
Qi-Dong
QD
Ma
Yan-Jun
YJ
Yang
Lan
L
Nie
Fei-Fei
FF
Gu
Hong-Yan
HY
Zhao
Li
L
Lu
Na
N
Qi
Qi
Q
Liu
Wei
W
Wang
Xiao-Tang
XT
Guo
Qing-Long
QL
D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D047368:Tumor Burden / Q000187:drug effects; D044004:Xanthones / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D051017:Apoptosis Regulatory Proteins; D044004:Xanthones; C052659:gambogic acid; D045304:Cytochromes c