Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells.
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)-alpha on neuronally differentiated PC-12 cells. PC-12 cells dead from exposure to TNF-alpha 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 microM crocin. Moreover, crocin suppressed the TNF-alpha-induced expression of Bcl-Xs and LICE mRNAs and simultaneously restored the cytokine-induced reduction of Bcl-X(L) mRNA expression. The modulating effects of crocin on the expression of Bcl-2 family proteins led to a marked reduction of a TNF-alpha-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.
Soeda
S
S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Ochiai
T
T
Paopong
L
L
Tanaka
H
H
Shoyama
Y
Y
Shimeno
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology*; D020170:Caspase 1 / Q000096:biosynthesis / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000276:immunology / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D003630:Daunorubicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D016716:PC12 Cells / Q000187:drug effects / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D051020:bcl-X Protein
C494813:Bcl2l1 protein, rat; D003574:Cytochrome c Group; D004365:Drugs, Chinese Herbal; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D002338:Carotenoids; C029036:crocin; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1; D003630:Daunorubicin