| 8-amino-adenosine Activates p53-Independent Cell Death of Metastatic Breast Cancers. | |
| | |
MedLine Citation:
|
PMID: 22973058 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
8-amino-adenosine (8-NH(2)-Ado) is a ribose sugar nucleoside analogue that reduces cellular ATP levels and inhibits mRNA synthesis. Estrogen receptor negative (ER-), metastatic breast cancers often contain mutant p53; therefore we asked if 8-NH(2)-Ado could kill breast cancer cells without activating the p53-pathway. Regardless of the breast cancer sub-type tested, or the p53 status of the cells, 8-NH(2)-Ado was more cytotoxic than either gemcitabine or etoposide. 8-NH(2)-Ado treatment inhibited cell proliferation, activated cell death, and did not activate transcription of the p53 target gene p21 or increase protein levels of either p53 or p21. This occurred in the estrogen receptor positive (ER+) MCF-7 cells that express wild-type p53, the ER+ T47-D cells that express mutant p53, and the ER- MDA-MB-468 cells or MDA-MB-231 cells that both express mutant p53. 8-NH(2)-Ado induced apoptotic death of MCF-7 cells and apoptosis was not inhibited by knockdown of functional p53. Moreover the pan-caspase inhibitor Z-VAD blocked the 8-NH(2)-Ado induced MCF-7 cell death. Interestingly 8-NH(2)-Ado caused the MDA-MB-231 cells to detach from the plate with only limited evidence of apoptotic cell death markers and the cell death was not inhibited by Z-VAD. Inhibition of MDA-MB-231 cell autophagy, by reduction of ATG7 or 3MA treatment, did not block this 8-NH(2)-Ado mediated cytotoxicity. Importantly 8-NH(2)-Ado was highly cytotoxic to triple negative breast cancer cells and worked through a pathway that did not require wild-type p53 for cytoxicity. Therefore, 8-NH(2)-Ado should be considered for the treatment of triple negative breast cancers that are chemotherapy resistant. |
| | |
Authors:
|
Alla Polotskaia; Sandy Hoffman; Nancy L Krett; Mala Shanmugam; Steven T Rosen; Jill Bargonetti |
Related Documents
:
|
22965878 - Folliculin interacts with p0071 (plakophilin-4) and deficiency is associated with disor... 23222438 - Dose-dependent roles for canonical wnt signalling in de novo crypt formation and cell c... 23060928 - Effect of jagged1 on the proliferation and migration of colon cancer cells. 21445448 - Tracking and synchronization of the yeast cell cycle using dielectrophoretic opacity. 22965878 - Folliculin interacts with p0071 (plakophilin-4) and deficiency is associated with disor... 14986318 - Cell seeding into calcium phosphate cement. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-9-12 |
Journal Detail:
|
Title: Molecular cancer therapeutics Volume: - ISSN: 1538-8514 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2012 Sep |
Date Detail:
|
Created Date: 2012-9-13 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
1Hunter College of the City University of New York, Hunter. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Epithelial-Mesenchymal Transition and Stem Cell Markers in Patients with HER2-Positive Metastatic Br...
Next Document: Cd2+ Block and Permeation in CaV3.1 (?1G) T-type Calcium Channels. A Candidate Mechanism for Cd2+ In...