Research article summary (published 21 Jun 2009):

Emodin has cytotoxic and protective effects in rat C6 glioma cells: roles of Mdr1a and nuclear factor kappaB in cell survival.

Full Abstract

1,3,8-Trihydroxy-6-methylanthaquinone (emodin) is recognized as an antiproliferative compound. In the present study, however, we show that emodin has both toxic and survival effects in glioma cells and that the survival effects involve Mdr1a. Emodin inhibited the proliferation and induced apoptosis of C6 cells in a 12-h treatment, but C6 cells survived a 72-h drug treatment, indicating resistance to emodin. Emodin-induced apoptosis was reduced by inhibition of the expression and activation of apoptosis-associated proteins including p53, Bax, Bcl-2, Fas, and caspase-3. C6 cells could express antioxidant proteins (superoxide dismutase and catalase) to decrease reactive oxygen species-induced cytotoxicity of emodin and overexpress multidrug resistance genes (Mdr1a, MRP2, MRP3, and MRP6) to decrease the intracellular accumulation of emodin. Electrophoretic mobility shift analysis showed that emodin decreased nuclear factor kappaB (NF-kappaB) expression in 24 h of treatment, but in 48 h, emodin increased NF-kappaB activity. A confocal microscope showed that emodin induced NF-kappaB translocation from cytoplasm to nuclei. C6 cells would activate the mitogen-activated protein kinase survival pathway and express the DNA repair gene (MGMT) and associated proteins (PARP and XRCC1) to recover the cell activity. C6 cells also expressed GRP78 to decrease emodin-induced endoplasmic reticulum (ER) stress that would cause apoptosis in C6 cells, and GRP78 inhibited the expression of GADD153 to enhance the expression of Bcl-2 that could balance the ER- and mitochondria-induced apoptosis of C6 cells.

Author information

Author/s: Kuo, Tzu-Ching (TC); Yang, Jai-Sing (JS); Lin, Meng-Wei (MW); Hsu, Shu-Chun (SC); Lin, Jen-Jyh (JJ); Lin, Hui-Ju (HJ); Hsia, Te-Chun (TC); Liao, Ching-Lung (CL); Yang, Mei-Due (MD); Fan, Ming-Jen (MJ); Wood, W G (WG); Chung, Jing-Gung (JG);

Affiliation: Department of Microbiology, China Medical University, 91, Hsueh-Shih Road, Taichung 404, Taiwan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther), published in United States. (Language: eng)

Reference: 2009-Sep; vol 330 (issue 3) : pp 736-44

Dates: Created 2009/08/21; Completed 2009/09/21;

PMID: 19549930, status: MEDLINE (last retrieval date: 9/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Antineoplastic Agents Apoptosis - drug effects Blotting, Western Calcium - metabolism Cell Line, Tumor Cell Survival - drug effects; physiology DNA Damage DNA Fragmentation - drug effects Electrophoretic Mobility Shift Assay Emodin - pharmacology

Fluoresceins Fluorescent Dyes Microscopy, Fluorescence NF-kappa B - physiology P-Glycoproteins - physiology Protective Agents Protein Kinase Inhibitors - pharmacology RNA, Small Interfering - genetics Rats Reactive Oxygen Species - metabolism Transfection

Associated Chemicals: Antineoplastic Agents (0) ; Fluoresceins (0) ; Fluorescent Dyes (0) ; NF-kappa B (0) ; P-Glycoproteins (0) ; Protective Agents (0) ; Protein Kinase Inhibitors (0) ; RNA, Small Interfering (0) ; Reactive Oxygen Species (0) ; multidrug resistance protein 3 (0) ; calcein AM (148504-34-1) ; Emodin (518-82-1) ; Calcium (7440-70-2)

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