Involvement of JNK-initiated p53 accumulation and phosphorylation of p53 in pseudolaric acid B induced cell death.
A terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay was used to determine that apoptosis causes HeLa cell death induced by pseudolaric acid B. The c-Jun N-terminal kinase (JNK) inhibitor SP600125 decreased p53 protein expression during exposure to pseudolaric acid B. SP600125 decreased the phosphorylation of p53 during pseudolaric acid B exposure, indicating that JNK mediates phosphorylation of p53 during the response to pseudolaric acid B. SP600125 reversed pseudolaric acid B-induced down-regulation of phosphorylated extracellular signal-regulated protein kinase (ERK), and protein kinase C (PKC) was activated by pseudolaric acid B, whereas staurosporine, calphostin C, and H7 partly blocked this effect. These results indicate that p53 is partially regulated by JNK in pseudolaric acid B-induced HeLa cell death and that PKC participates in pseudolaric acid B-induced HeLa cell death.
Gong
Xianfeng
X
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
Wang
Minwei
M
Tashiro
Shin-ichi
S
Onodera
Satoshi
S
Ikejima
Takashi
T
D000873:Anthracenes / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*
D000873:Anthracenes; D004224:Diterpenes; D016159:Tumor Suppressor Protein p53; C432165:pyrazolanthrone; C058391:pseudolaric acid B; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases