Pseudolaric acid B induces apoptosis via activation of c-Jun N-terminal kinase and caspase-3 in HeLa cells.
- Author:
Xianfeng GONG
1
;
Minwei WANG
;
Zhen WU
;
Shin ichi TASHIRO
;
Satoshi ONODERA
;
Takashi IKEJIMA
Author Information
1. China-Japan Research Institute of Medical Pharmaceutical Sciences ikejimat@vip.sina.com
- Publication Type:Original Article
- Keywords:
apoptosis;
caspase;
HeLa;
MAPK;
pseudolaric acid B
- MeSH:
Anthracenes/pharmacology;
*Apoptosis;
Caspases/antagonists & inhibitors/*metabolism;
Cell Proliferation/drug effects;
Cysteine Proteinase Inhibitors/pharmacology;
Diterpenes/*pharmacology;
Down-Regulation;
Enzyme Activation;
Hela Cells;
Humans;
JNK Mitogen-Activated Protein Kinases/drug effects/*metabolism;
Oligopeptides/pharmacology;
Protein Kinase Inhibitors/pharmacology;
Proto-Oncogene Proteins c-bcl-2/metabolism;
Signal Transduction/*drug effects;
Up-Regulation
- From:Experimental & Molecular Medicine
2004;36(6):551-556
- CountryRepublic of Korea
- Language:English
-
Abstract:
Pseudolaric acid B was isolated from Pseudolarix kaempferi Gordon (Pinaceae) and was evaluated for the anti-cancer effect in HeLa cells. We observed that pseudolaric acid B inhibited cell proliferation and induced apoptosis in a time- and dose-dependent manner. HeLa cells treated with pseudolaric acid B showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. JNK inhibitor, SP600125, markedly inhibited pseudolaric acid B-induced cell death. In addition, Bcl-2 expression was down-regulated while Bax protein level was up-regulated. Caspase-3 inhibitor, z-DEVD-fmk, partially blocked pseudolaric acid B-induced cell death, and the expression of two classical caspase substrates, PARP and ICAD, were both decreased in a time- dependent manner, indicative of downstream caspase activation.
