Synthetic retinoid CD437 induces apoptosis and acts synergistically with TRAIL receptor-2 agonist in malignant melanoma
| Autor: | Vivi Ann Flørenes, Birgit Engesæter, Elisabeth Emilsen, Anne Katrine Ree Rosnes, Hiep Phuc Dong, Gry Irene Magnussen, Susan Shahzidi |
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| Rok vydání: | 2012 |
| Předmět: |
Cell cycle checkpoint
Skin Neoplasms medicine.drug_class Lexatumumab Cell Survival Biophysics Cathepsin D Antineoplastic Agents Apoptosis Caspase 8 Biochemistry Retinoids Cell Line Tumor medicine Humans Retinoid RNA Messenger fas Receptor Molecular Biology Melanoma Caspase biology Antibodies Monoclonal Drug Synergism Cell Biology Caspase 9 Cell biology Up-Regulation Receptors TNF-Related Apoptosis-Inducing Ligand Cell culture biology.protein Poly(ADP-ribose) Polymerases Transcription Factor CHOP medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 420(3) |
| ISSN: | 1090-2104 |
| Popis: | The novel synthetic retinoid, CD437, shows potent anti-tumor activity in a range of different cancer cell lines and now serves as a prototype for development of new retinoid related molecules (RRMs). The purpose of this study was to examine the effect and cellular targets of CD437 in the human metastatic melanoma cell lines FEMX-1 and WM239. We showed that treatment with CD437 led to cell cycle arrest and induced apoptosis through both the extrinsic- and intrinsic pathways (caspase 8, -9 and PARP cleavage) in both cell lines. Interestingly, apoptosis was induced independently of DNA-fragmentation in FEMX-1 cells, and appeared partially caspase-independent in the WM239 cells. Additionally, up-regulation of CHOP mRNA and cathepsin D protein expression, following retinoid treatment, suggests involvement of the endoplasmatic reticulum (ER) and lysosomes, respectively. Combination of suboptimal concentrations of CD437 and lexatumumab, a TRAIL death receptor-2 agonist, resulted in synergistic reduction of viable cells, along with increased PARP cleavage. These results indicate that CD437 has a strong anti-neoplastic effect alone and in combination with lexatumumab in melanoma cell lines. |
| Databáze: | OpenAIRE |
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