التفاصيل البيبلوغرافية
العنوان: |
Bak Compensated for Bax in p53-null Cells to Release Cytochrome c for the Initiation of Mitochondrial Signaling during Withanolide D-Induced Apoptosis |
المؤلفون: |
Susmita Mondal, Kaushik Bhattacharya, Asish Mallick, Rajender Sangwan, Chitra M |
المساهمون: |
The Pennsylvania State University CiteSeerX Archives |
المصدر: |
ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/f2/65/PLoS_One_2012_Mar_29_7(3)_e34277.tar.gz |
المجموعة: |
CiteSeerX |
الوصف: |
The goal of cancer chemotherapy to induce multi-directional apoptosis as targeting a single pathway is unable to decrease all the downstream effect arises from crosstalk. Present study reports that Withanolide D (WithaD), a steroidal lactone isolated from Withania somnifera, induced cellular apoptosis in which mitochondria and p53 were intricately involved. In MOLT-3 and HCT116p53+/+ cells, WithaD induced crosstalk between intrinsic and extrinsic signaling through Bid, whereas in K562 and HCT116p532/2 cells, only intrinsic pathway was activated where Bid remain unaltered. WithaD showed pronounced activation of p53 in cancer cells. Moreover, lowered apoptogenic effect of HCT116p532/2 over HCT116p53+/+ established a strong correlation between WithaD-mediated apoptosis and p53. WithaD induced Bax and Bak upregulation in HCT116p53+/+, whereas increase only Bak expression in HCT116p532/2 cells, which was coordinated with augmented p53 expression. p53 inhibition substantially reduced Bax level and failed to inhibit Bak upregulation in HCT116p53+/+ cells confirming p53-dependent Bax and p53-independent Bak activation. Additionally, in HCT116p53+/+ cells, combined loss of Bax and Bak (HCT116Bax2Bak2) reduced WithaD-induced apoptosis and completely blocked cytochrome c release whereas single loss of Bax or Bak (HCT116Bax2Bak+/HCT116Bax+Bak2) was only marginally effective after WithaD treatment. In HCT116p532/2 cells, though Bax translocation to mitochondria was abrogated, Bak oligomerization helped the cells to release cytochrome c even before the disruption of mitochondrial membrane potential. WithaD also showed in |
نوع الوثيقة: |
text |
وصف الملف: |
application/zip |
اللغة: |
English |
العلاقة: |
http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.271.674Test |
حقوق: |
Metadata may be used without restrictions as long as the oai identifier remains attached to it. |
رقم الانضمام: |
edsbas.BAC2FCF2 |
قاعدة البيانات: |
BASE |