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A small molecule Smac mimic potentiates TRAIL-mediated cell death of ovarian cancer cells.
- Source :
-
Gynecologic oncology [Gynecol Oncol] 2007 May; Vol. 105 (2), pp. 481-92. Date of Electronic Publication: 2007 Feb 09. - Publication Year :
- 2007
-
Abstract
- Objectives: Ovarian cancer remains a leading cause of death in women and development of new therapies is essential. Second mitochondria derived activator of caspase (Smac) has been described to sensitize for apoptosis. We have explored the proapoptotic activity of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines (A2780 cells and its chemoresistant derivatives A2780/ADR and A2780/DDP), cancer cell lines and in primary ovarian cancer cells.<br />Methods: The effects of a small molecule mimic of Smac/DIABLO on ovarian cancer cell lines and primary ovarian cancer cells were determined by cell proliferation, apoptosis and biochemical assays.<br />Results: This compound added alone elicited only a weak proapoptotic effect; however, it strongly synergizes with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAILR2 antibody (Lexatumumab) in inducing apoptosis of ovarian cancer cells.<br />Conclusions: These observations suggest that small molecule mimic of Smac/DIABLO could be useful for the development of experimental strategies aiming to treat ovarian cancer. Interestingly, in addition to its well known proapoptotic effects, Smac/DIABLO elicited a significant increase of pro-caspase-3 levels.
- Subjects :
- Antibodies, Monoclonal pharmacology
Antibodies, Monoclonal, Humanized
Apoptosis drug effects
Apoptosis Regulatory Proteins metabolism
Biomimetic Materials administration & dosage
Biomimetic Materials pharmacology
Caspase 3 metabolism
Caspase 9 metabolism
Cell Growth Processes drug effects
Cell Line, Tumor
Diynes administration & dosage
Drug Synergism
Enzyme Activation drug effects
Female
Humans
Intracellular Signaling Peptides and Proteins
Mitochondrial Proteins
Ovarian Neoplasms metabolism
Ovarian Neoplasms pathology
Peptide Fragments administration & dosage
Peptide Fragments pharmacology
Receptors, TNF-Related Apoptosis-Inducing Ligand agonists
Receptors, Tumor Necrosis Factor agonists
TNF-Related Apoptosis-Inducing Ligand administration & dosage
Tetrazoles administration & dosage
X-Linked Inhibitor of Apoptosis Protein metabolism
Antineoplastic Combined Chemotherapy Protocols pharmacology
Diynes pharmacology
Ovarian Neoplasms drug therapy
TNF-Related Apoptosis-Inducing Ligand pharmacology
Tetrazoles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0090-8258
- Volume :
- 105
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Gynecologic oncology
- Publication Type :
- Academic Journal
- Accession number :
- 17292950
- Full Text :
- https://doi.org/10.1016/j.ygyno.2007.01.011