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Role of JNK and p38 MAPK in Taiwanin A induced cell death
Author(s) -
yeh sheau farn
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.712.1
Subject(s) - p38 mitogen activated protein kinases , apoptosis , microbiology and biotechnology , phosphorylation , cytotoxicity , mapk/erk pathway , kinase , chemistry , protein kinase a , biology , biochemistry , in vitro
Taiwanin A, a lignan isolated from Taiwania cryptomerioides Hayata, has been reported to have cytotoxicity against human cancer cells. It was shown that Taiwanin A damages microtubule, induces mitotic arrest and apoptosis. Taiwanin A induced apoptosis in HepG2 cells was mediated through activating the tumor suppressor protein p53. However, whether there are other intracellular signaling pathways also involved in Taiwanin A mediated apoptosis is not known. In this study, we examined the activation of three MAPKs (mitogen activated protein kinase): ERK, p38 and JNK in HepG2 cells upon Taiwanin A treatment and the role of MAPK activation in Taiwanin A induced apoptosis. We found that Taiwanin A activated all three MAPKs. Taiwanin A induced cytotoxicity could be partially blocked by either the p38 inhibitor SB203580 or JNK inhibitor SP600125, but not by ERK inhibitor PD98059. Combined treatment of SB203580 and SP600125 showed additive effects on the inhibition of Taiwanin A's cytotoxicity suggested that both JNK and p38 may play role in Taiwanin A induced apoptosis. Inhibition of p38 activity reduced Taiwanin A‐induced p53 phosphorylation on serine 15 residue. Direct interaction of Taiwanin A activated p38 and p53 was demonstrated by immuno‐precipitation. On the other hand, inhibition of JNK activity by either SP600125 or by silencing the JNK scaffold protein JIP2 was also shown to reduce phosphorylation of Bcl‐2. Therefore, we identified two Taiwanin A induced signaling pathways; p38‐p53 and JNK‐Bcl‐2; that are involved in Taiwanin A induced apoptosis in HepG2 cells.