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CCT327 enhances TRAIL-induced apoptosis through the induction of death receptors and downregulation of cell survival proteins in TRAIL-resistant human leukemia cells
- Source :
- Oncology Reports. 32:1257-1264
- Publication Year :
- 2014
- Publisher :
- Spandidos Publications, 2014.
-
Abstract
- Tumor necrosis factor-related apoptosis‑inducing ligand (TRAIL) has potential application in cancer therapy and it has the ability to selectively kill cancer cells without affecting normal cells. However, the development of resistance to TRAIL in cancer cells cannot be avoided. This study investigated the effects of 2-(5-methylselenophen‑2‑yl)‑6,7‑methylenedioxyquinolin‑4-one (CCT327), an analogue of quinolin-4-one, on the sensitization of cancer cells to TRAIL and on TRAIL‑induced apoptosis in TRAIL‑resistance human leukemia cells (HL60‑TR). We found that CCT327 enhanced TRAIL‑induced apoptosis through upregulation of death receptors DR4 and DR5. In addition to upregulating DRs (death receptors), CCT327 suppressed the expression of decoy receptor DcR1 and DcR2. CCT327 significantly downregulated the expression of FLICE inhibitory protein (cFLIP) and other antiapoptotic proteins. We also demonstrated that CCT327 could activate p38 and JNK. Moreover, CCT327-induced induction of DR5 and DR4 was mediated by reactive oxygen species (ROS), and N-acetylcysteine (NAC) blocked the induction of DRs by CCT327. Taken together, these results showed that CCT327 combined with TRAIL treatment may provide an effective therapeutic strategy for cancer.
- Subjects :
- Cancer Research
HL60
CASP8 and FADD-Like Apoptosis Regulating Protein
Antineoplastic Agents
Apoptosis
HL-60 Cells
Quinolones
Biology
TNF-Related Apoptosis-Inducing Ligand
chemistry.chemical_compound
Downregulation and upregulation
Organoselenium Compounds
Humans
Receptor
Cell Proliferation
Leukemia
Oncogene
Receptors, Death Domain
General Medicine
Acetylcysteine
Up-Regulation
Cell biology
Oncology
chemistry
Drug Resistance, Neoplasm
Cancer cell
Quinolines
Tumor necrosis factor alpha
Reactive Oxygen Species
A431 cells
Subjects
Details
- ISSN :
- 17912431 and 1021335X
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Oncology Reports
- Accession number :
- edsair.doi.dedup.....906edca23a0cdff531a0c5453f1343a3