TY - JOUR
T1 - Crocin suppresses tumor necrosis factor-α-induced cell death of neuronally differentiated PC-12 cells
AU - Soeda, Shinji
AU - Ochiai, Takashi
AU - Paopong, Loungratana
AU - Tanaka, Hiroyuki
AU - Shoyama, Yukihiro
AU - Shimeno, Hiroshi
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Science, Sports and Culture of Japan and by funds from the Central Research Institute of Fukuoka University.
PY - 2001/11/2
Y1 - 2001/11/2
N2 - Crocus sativus L. is used in Chinese traditional medicine to treat some disorders of the central nervous system. Crocin is an ethanol-extractable component of Crocus sativus L.; it is reported to prevent ethanol-induced impairment of learning and memory in mice. In this study, we demonstrate that crocin suppresses the effect of tumor necrosis factor (TNF)-α on neuronally differentiated PC-12 cells. PC-12 cells dead from exposure to TNF-α show apoptotic morphological changes and DNA fragmentation. These hallmark features of cell death did not appear in cells treated in the co-presence of 10 μM crocin. Moreover, crocin suppressed the TNF-α-induced expression of Bcl-XS and LICE mRNAs and simultaneously restored the cytokine-induced reduction of Bcl-XL mRNA expression. The modulating effects of crocin on the expression of Bcl-2 family proteins led to a marked reduction of a TNF-α-induced release of cytochrome c from the mitochondria. Crocin also blocked the cytochrome c-induced activation of caspase-3. To learn how crocin exhibits these anti-apoptotic actions in PC-12 cells, we tested the effect of crocin on PC-12 cell death induced by daunorubicin. We found that crocin inhibited the effect of daunorubicin as well. Our findings suggest that crocin inhibits neuronal cell death induced by both internal and external apoptotic stimuli.
AB - Crocus sativus L. is used in Chinese traditional medicine to treat some disorders of the central nervous system. Crocin is an ethanol-extractable component of Crocus sativus L.; it is reported to prevent ethanol-induced impairment of learning and memory in mice. In this study, we demonstrate that crocin suppresses the effect of tumor necrosis factor (TNF)-α on neuronally differentiated PC-12 cells. PC-12 cells dead from exposure to TNF-α show apoptotic morphological changes and DNA fragmentation. These hallmark features of cell death did not appear in cells treated in the co-presence of 10 μM crocin. Moreover, crocin suppressed the TNF-α-induced expression of Bcl-XS and LICE mRNAs and simultaneously restored the cytokine-induced reduction of Bcl-XL mRNA expression. The modulating effects of crocin on the expression of Bcl-2 family proteins led to a marked reduction of a TNF-α-induced release of cytochrome c from the mitochondria. Crocin also blocked the cytochrome c-induced activation of caspase-3. To learn how crocin exhibits these anti-apoptotic actions in PC-12 cells, we tested the effect of crocin on PC-12 cell death induced by daunorubicin. We found that crocin inhibited the effect of daunorubicin as well. Our findings suggest that crocin inhibits neuronal cell death induced by both internal and external apoptotic stimuli.
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U2 - 10.1016/S0024-3205(01)01357-1
DO - 10.1016/S0024-3205(01)01357-1
M3 - Article
C2 - 11720092
AN - SCOPUS:0035798068
SN - 0024-3205
VL - 69
SP - 2887
EP - 2898
JO - Life Sciences
JF - Life Sciences
IS - 24
ER -