Back to Search
Start Over
YM155 potently triggers cell death in breast cancer cells through an autophagy-NF-kB network.
- Source :
-
Oncotarget [Oncotarget] 2015 May 30; Vol. 6 (15), pp. 13476-86. - Publication Year :
- 2015
-
Abstract
- Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first "Survivin suppressant" but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. We herein show that YM155 exerts single agent toxicity on primary breast cancer cells grown in an ex vivo assay preserving tumor microenvironment. In vitro assays indicate that YM155 more efficiently triggers cell death in breast cancer cells (including these with stem-cell like properties) than in non tumorigenic mammary cells. YM155-induced cell death is critically dependent on autophagy and NF-kB but independent of p53 and it coïncides with DNA damage and a DNA damage response in p53-proficient cells. Our results point out a crosstalk between NF-kB and autophagy controlling YM155-induced death in breast cancer cells and argue for the potential use of YM155 as a genotoxic agent in breast cancer therapy.
- Subjects :
- Antineoplastic Agents pharmacology
Autophagy drug effects
Breast Neoplasms genetics
Breast Neoplasms metabolism
Breast Neoplasms pathology
Cell Death drug effects
Cell Line, Tumor
Cell Proliferation drug effects
DNA Damage
Female
Humans
MCF-7 Cells
NF-kappa B antagonists & inhibitors
Signal Transduction drug effects
Transfection
Xenograft Model Antitumor Assays
Breast Neoplasms drug therapy
Imidazoles pharmacology
NF-kappa B metabolism
Naphthoquinones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 25974963
- Full Text :
- https://doi.org/10.18632/oncotarget.3638