Emodin has cytotoxic and protective effects in rat C6 glioma cells: Roles of Mdr1a and nuclear factor κB in cell survival

Tzu Ching Kuo, Jai Sing Yang, Meng Wei Lin, Shu Chun Hsu, Jen Jyh Lin, Hui Ju Lin, Te Chun Hsia, Ching Lung Liao, Mei Due Yang, Ming Jen Fan, W. G. Wood, Jing Gung Chung

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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 κB (NF-κB) expression in 24 h of treatment, but in 48 h, emodin increased NF-κB activity. A confocal microscope showed that emodin induced NF-κB 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.

Original languageEnglish (US)
Pages (from-to)736-744
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume330
Issue number3
DOIs
StatePublished - Sep 21 2009

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