TY - JOUR
T1 - Emodin has cytotoxic and protective effects in rat C6 glioma cells
T2 - Roles of Mdr1a and nuclear factor κB in cell survival
AU - Kuo, Tzu Ching
AU - Yang, Jai Sing
AU - Lin, Meng Wei
AU - Hsu, Shu Chun
AU - Lin, Jen Jyh
AU - Lin, Hui Ju
AU - Hsia, Te Chun
AU - Liao, Ching Lung
AU - Yang, Mei Due
AU - Fan, Ming Jen
AU - Wood, W. G.
AU - Chung, Jing Gung
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70349126349&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349126349&partnerID=8YFLogxK
U2 - 10.1124/jpet.109.153007
DO - 10.1124/jpet.109.153007
M3 - Article
C2 - 19549930
AN - SCOPUS:70349126349
SN - 0022-3565
VL - 330
SP - 736
EP - 744
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 3
ER -