Your browser doesn't support javascript.
loading
Bim directly antagonizes Bcl-xl in doxorubicin-induced prostate cancer cell apoptosis independently of p53.
Yang, Min-Chi; Lin, Ru-Wei; Huang, Shih-Bo; Huang, Shin-Yuan; Chen, Wen-Jie; Wang, Shiaw; Hong, Yi-Ren; Wang, Chihuei.
Afiliación
  • Yang MC; a Department of Biotechnology , Kaohsiung Medical University , Kaohsiung , Taiwan.
  • Lin RW; a Department of Biotechnology , Kaohsiung Medical University , Kaohsiung , Taiwan.
  • Huang SB; a Department of Biotechnology , Kaohsiung Medical University , Kaohsiung , Taiwan.
  • Huang SY; a Department of Biotechnology , Kaohsiung Medical University , Kaohsiung , Taiwan.
  • Chen WJ; a Department of Biotechnology , Kaohsiung Medical University , Kaohsiung , Taiwan.
  • Wang S; b Hsueh-Shih Clinic , Taichung , Taiwan.
  • Hong YR; c Department of Biochemistry & Graduate Institute of Medicine, Medical University , Kaohsiung , Taiwan.
  • Wang C; a Department of Biotechnology , Kaohsiung Medical University , Kaohsiung , Taiwan.
Cell Cycle ; 15(3): 394-402, 2016.
Article en En | MEDLINE | ID: mdl-26694174
Doxorubicin and other anthracycline compounds exert their anti-cancer effects by causing DNA damage and initiating cell cycle arrest in cancer cells, followed by apoptosis. DNA damage generally activates a p53-mediated pathway to initiate apoptosis by increasing the level of the BH3-only protein, Puma. However, p53-mediated apoptosis in response to DNA damage has not yet been validated in prostate cancers. In the current study, we used LNCaP and PC3 prostate cancer cells, representing wild type p53 and a p53-null model, to determine if DNA damage activates p53-mediated apoptosis in prostate cancers. Our results revealed that PC3 cells were 4 to 8-fold less sensitive than LNCaP cells to doxorubicin-inuced apoptosis. We proved that the differential response of LNCaP and PC3 to doxorubicin was p53-independent by introducing wild-type or dominant negative p53 into PC3 or LNCaP cells, respectively. By comparing several apoptosis-related proteins in both cell lines, we found that Bcl-xl proteins were much more abundant in PC3 cells than in LNCaP cells. We further demonstrated that Bcl-xl protects LNCaP and PC3 cells from doxorubicin-induced apoptosis by using ABT-263, an inhibitor of Bcl-xl, as a single agent or in combination with doxorubicin to treat LNCaP or PC3 cells. Bcl-xl rather than p53, likely contributes to the differential response of LNCaP and PC3 to doxorubicin in apoptosis. Finally, co-immunoprecipitation and siRNA analysis revealed that a BH3-only protein, Bim, is involved in doxorubicin-induced apoptosis by directly counteracting Bcl-xl.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Doxorrubicina / Proteína p53 Supresora de Tumor / Apoptosis / Proteína bcl-X / Proteína 11 Similar a Bcl2 Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Cell Cycle Año: 2016 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Doxorrubicina / Proteína p53 Supresora de Tumor / Apoptosis / Proteína bcl-X / Proteína 11 Similar a Bcl2 Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Cell Cycle Año: 2016 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos