Mechanisms for 2‐methoxyestradiol‐induced apoptosis of prostate cancer cells

FEBS Letters

Bu, Shizhong³  Blaukat, Andree³  Heldin, Nils-Erik¹  Landström, Maréne³  Fu, Xin² 

[1] Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden;Department of Women's and Children's Health, Obstetrics and Gynaecology, Uppsala University, SE-751 85 Uppsala, Sweden;Ludwig Institute for Cancer Research, Biomedical Center, Box 595, SE-75124 Uppsala, Sweden

关键词: Apoptosis;    Bcl-2;    Breast cancer;    2-Methoxyestradiol;    Prostate cancer;    Stress-activated protein kinase/c-Jun N-terminal kinase;    ERK;    extracellular signal-regulated kinase;    GPCR;    G protein-coupled receptor;    JNK;    c-Jun N-terminal kinase;    MAPK;    mitogen-activated protein kinase;    2-ME;    2-methoxyestradiol;    Ptx;    pertussis toxin;    SAPK;    stress-activated protein kinase;    TUNEL;    terminal deoxynucleotide transferase-mediated dUTP nick-end labeling;   

DOI  :  10.1016/S0014-5793(02)03478-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Prostate and breast carcinomas are sex hormone-related carcinomas, which are known to be associated with an over-expression of the proto-oncogene Bcl-2. Here, we report that 2-methoxyestradiol (2-ME), an endogenous metabolite of estrogen that does not bind to nuclear estrogen receptors, effectively induces apoptosis in Bcl-2-expressing human prostate and breast carcinoma cells in vitro and in a rat prostate tumor model in vivo. In several cell lines derived from prostate, breast, liver and colorectal carcinomas, 2-ME treatment led to an activation of c-Jun N-terminal kinase (JNK) and phosphorylation of Bcl-2, which preceded the induction of apoptosis. In summary, our data suggest that 2-ME induces apoptosis in epithelial carcinomas by causing phosphorylation of JNK, which appears to be correlated with phosphorylation of Bcl-2.

【 授权许可】

Unknown