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

in Cellular and molecular life sciences : CMLS by S Mijatovic, D Maksimovic-Ivanic, J Radovic, Dj Miljkovic, Lj Harhaji, O Vuckovic, S Stosic-Grujicic, M Mostarica Stojkovic, V Trajkovic

TLDR

  • The study found that aloe emodin (AE) can make glioma cells die in two ways: apoptosis (programmed cell death) and autophagy (a process where cells break down their own waste). AE also made the surviving glioma cells turn into astrocytes (a type of brain cell). The study found that AE did this by inhibiting a protein called ERK1/2, which is usually activated in glioma cells. A selective inhibitor of ERK1/2 activation, PD98059, mimicked the effects of AE on glioma cells. These findings suggest that AE can be used as an anti-glioma agent because it can make glioma cells die and turn into astrocytes.

Abstract

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.

Overview

  • The study investigates the effect of aloe emodin (AE) on the rat C6 glioma cell line. The hypothesis being tested is whether AE can induce apoptosis and autophagy in glioma cells and differentiate them into astrocytes. The methodology used includes cell cycle analysis, caspase-dependent apoptosis assay, intracytoplasmic acidic vesicle formation, and morphological changes. The primary objective of the study is to determine the anti-glioma action of AE and its underlying mechanisms.

Comparative Analysis & Findings

  • AE led to cell cycle block, caspasedependent apoptosis, and intracytoplasmic acidic vesicle formation, indicating autophagy in rat C6 glioma cells. The study also found that AE induced differentiation of surviving cells into astrocytes, as 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. These findings suggest 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.

Implications and Future Directions

  • The study highlights the potential of AE as an anti-glioma agent due to its ability to induce apoptosis, autophagy, and differentiation of glioma cells. The findings also provide insights into the underlying mechanisms of AE's anti-glioma action, which may inform the development of new therapeutic strategies for glioma. Future research should further explore the role of ERK in the anti-glioma action of AE and investigate the potential of AE in combination with other anti-glioma agents. Additionally, studies should be conducted to determine the safety and efficacy of AE in preclinical and clinical settings.
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