Cellular signalling, 2002-06, Vol.14 (6), p.509-515
2002
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- Autor(en) / Beteiligte
- Titel
- Modes of activation of mitogen-activated protein kinases and their roles in cepharanthine-induced apoptosis in human leukemia cells
- Ist Teil von
- Cellular signalling, 2002-06, Vol.14 (6), p.509-515
- Ort / Verlag
- England: Elsevier Inc
- Erscheinungsjahr
- 2002
- Quelle
- Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)
- Beschreibungen/Notizen
- We previously showed that cepharanthine (CEP), a biscoclaurine alkaloid, induces caspase-dependent and Fas-independent apoptosis in Jurkat and K562 human leukemia cells. In the present study, we investigated the effect of CEP on three groups of human mitogen-activated protein kinases (MAPKs) in relation to CEP-induced apoptosis. CEP, at the concentration required for and at the time of induction of apoptosis, activated MAPKs p38 in both Jurkat and K562 cells and activated extracellular signal-regulated kinases (ERKs) only in K562 cells. However, CEP treatment did not trigger c-Jun NH 2-terminal kinases (JNKs) activation. CEP increased the expression and phosphorylation levels of c-Jun and ATF-2 transcription factors. zVAD-fmk, a general caspase inhibitor, did not inhibit CEP-triggered p38 activation in Jurkat and K562 cells or ERK activation in K562 cells. Unexpectedly, pretreatment with a specific p38 inhibitor, SB203580, promoted CEP-induced apoptosis and caspase activation in Jurkat and K562 cells, whereas pretreatment with an MEK-1 inhibitor PD98059 inhibited CEP-induced apoptosis and caspase activation in K562 cells. A selective tyrosine kinase inhibitor, herbimycin A, which completely inhibited CEP-triggered ERKs activation, clearly promoted CEP-induced c-Jun expression and phosphorylation. Our results suggest that each of the three groups of MAP family members is uniquely involved in the CEP-mediated signal cascades in two different leukemia cell lines for inducing/regulating caspase activation and DNA fragmentation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0898-6568eISSN: 1873-3913DOI: 10.1016/S0898-6568(01)00278-9Titel-ID: cdi_proquest_miscellaneous_71531718
- Format
- –
- Schlagworte
- Alkaloids - antagonists & inhibitors, Alkaloids - pharmacology, Amino Acid Chloromethyl Ketones - pharmacology, Antineoplastic Agents, Phytogenic - antagonists & inhibitors, Antineoplastic Agents, Phytogenic - pharmacology, Apoptosis, Benzylisoquinolines, Caspase Inhibitors, Cepharanthine, Cysteine Proteinase Inhibitors - pharmacology, Enzyme Activation, Enzyme Inhibitors - pharmacology, ERK, Human leukemia cell, Humans, JNK, Jurkat Cells, K562 Cells, Kinetics, Leukemia - enzymology, Leukemia - pathology, MAP kinase, MAP Kinase Signaling System - drug effects, Mitogen-Activated Protein Kinases - antagonists & inhibitors, Mitogen-Activated Protein Kinases - metabolism, Mitogen-Activated Protein Kinases - physiology, p38, p38 Mitogen-Activated Protein Kinases, Phosphorylation, Protein-Tyrosine Kinases - antagonists & inhibitors, Transcription Factors - metabolism