Anti-glioma action of aloe emodin: the role of ERK inhibition

• Published in: Cellular and molecular life sciences : CMLS 2005-03, Vol.62 (5), p.589-598
• Main Authors: Mijatovic, S, Maksimovic-Ivanic, D, Radovic, J, Miljkovic, Dj, Harhaji, Lj, Vuckovic, O, Stosic-Grujicic, S, Mostarica Stojkovic, M, Trajkovic, V
• Format: Article
• Language: English
• Subjects: Aloe; Animals; Anthraquinone; Anthraquinones; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Autolysis; Autophagy; Cell activation; Cell cycle; Cell death; Cell differentiation; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Line, Tumor; Cell morphology; Cellular biology; Differentiation; Emodin; Emodin - pharmacology; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors; Extracellular Signal-Regulated MAP Kinases - physiology; Glial fibrillary acidic protein; Glioma - enzymology; Glioma cells; Kinases; MAP kinase; mitogen-activated protein kinase; Morphology; NF-κB protein; Proteins; Rats; Transcription activation; transcription factor NF-kappa B
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-005-4425-8

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-κB, 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.