Combined treatment with the Cox-2 inhibitor niflumic acid and PPARγ ligand ciglitazone induces ER stress/caspase-8-mediated apoptosis in human lung cancer cells
| Autor: | Byeong Mo Kim, Kyungah Maeng, Sung Hee Hong, Kee-Ho Lee |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Lung Neoplasms Blotting Western Apoptosis Cell Separation CHOP Pharmacology Caspase 8 Endoplasmic Reticulum Ligands Transfection Ciglitazone Cell Line Tumor Pparγ ligand Antineoplastic Combined Chemotherapy Protocols medicine Humans Chemistry Reverse Transcriptase Polymerase Chain Reaction Niflumic acid Niflumic Acid Drug Synergism Flow Cytometry PPAR gamma Oncology Cyclooxygenase 2 Unfolded protein response COX-2 inhibitor Thiazolidinediones medicine.drug |
| Zdroj: | Cancer letters. 300(2) |
| ISSN: | 1872-7980 |
| Popis: | The present study was performed to investigate the possible combined use of the Cox-2 inhibitor niflumic acid and the PPARγ ligand ciglitazone and to elucidate the mechanisms underlying enhanced apoptosis by this combination treatment in human lung cancer cells. Combined niflumic acid–ciglitazone treatment synergistically induced apoptotic cell death, activated caspase-9, caspase-3, and induced caspase-3-mediated PARP cleavage. The combination treatment also triggered apoptosis through caspase-8/Bid/Bax activation, and the inhibition of caspase-8 suppressed caspase-8/Bid activation, caspase-3-mediated PARP cleavage, and concomitant apoptosis. In addition, combined niflumic acid–ciglitazone treatment significantly induced ER stress responses, and suppression of CHOP expression significantly attenuated the combined niflumic acid–ciglitazone treatment-induced activation of caspase-8 and caspase-3, and the subsequent apoptotic cell death, indicating a role of ER stress in caspase-8 activation and apoptosis. Interestingly, the pro-apoptotic effects of combined niflumic acid–ciglitazone treatment were realized through Cox-2- and PPARγ-independent mechanisms. Taken together, these results suggest that sequential ER stress and caspase-8 activation are critical in combined niflumic acid–ciglitazone treatment-induced apoptosis in human lung cancer cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect