Anti-glioma action of aloe emodin: the role of ERK inhibition.
The effect of aloe emodin (AE), a herbal anthraquinone derivative, on the rat C6 glioma cell line was investigated. In addition to cell cycle block and caspasedependent apoptosis, AE led to the formation of intracytoplasmic acidic vesicles indicative for autophagic cell death. Moreover, differentiation of surviving cells toward the astrocytic lineage was confirmed by typical morphological changes and increased expression of glial fibrillary acidic protein (GFAP). AE did not affect the activation of mitogen-activated protein kinase p38, Jun-N-terminal kinase, or transcription factor NF-kappaB, but markedly inhibited the activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in C6 cells. A selective inhibitor of ERK activation, PD98059, mimicked the effects of AE on glioma cell morphology and GFAP expression, but failed to induce either apoptosis or autophagy. Taken together, these results indicate that the anti-glioma action of AE involves ERK-independent induction of both apoptosis and autophagy, as well as ERK inhibition-mediated differentiation of glioma cells.
Mijatovic
S
S
Institute for Biological Research, Despota Stefana 142, 11000, Belgrade, Serbia and Montenegro. mamas@yubc.net
Maksimovic-Ivanic
D
D
Radovic
J
J
Miljkovic
Dj
Dj
Harhaji
Lj
Lj
Vuckovic
O
O
Stosic-Grujicic
S
S
Mostarica Stojkovic
M
M
Trajkovic
V
V
D000818:Animals; D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D001329:Autolysis; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D004642:Emodin / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D005910:Glioma / Q000201:enzymology*; D051381:Rats
D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; C518327:aloe emodin; D048049:Extracellular Signal-Regulated MAP Kinases; D004642:Emodin