Selected genes down-regulated in DU145 and PC-3 cells (prostate cancer) after treatment with the NSAID (non-steroid anti-inflammatory drug) sulindac [PubChem=5352].
| PAG Title | Selected genes down-regulated in DU145 and PC-3 cells (prostate cancer) after treatment with the NSAID (non-steroid anti-inflammatory drug) sulindac [PubChem=5352]. |
| PAG ID | MAX003295 |
| Type | A |
| Source Link |  MSigDB |
| Publication Reference | NA |
| PAG Description | Numerous studies show that nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in chemoprevention or treatment of cancer. Nevertheless, the mechanisms underlying these antineoplastic effects remain poorly understood. Here, we report that induction of the cancer-specific proapoptotic cytokine melanoma differentiation associated gene-7/interleukin-24 (MDA-7/IL-24) by several NSAIDs is an essential step for induction of apoptosis and G(2)-M growth arrest in cancer cells in vitro and inhibition of tumor growth in vivo. We also show that MDA-7/IL-24-dependent up-regulation of growth arrest and DNA damage inducible 45 alpha (GADD45alpha) and GADD45gamma gene expression is sufficient for cancer cell apoptosis via c-Jun NH(2)-terminal kinase (JNK) activation and growth arrest induction through inhibition of Cdc2-cyclin B checkpoint kinase. Knockdown of GADD45alpha and GADD45gamma transcription by small interfering RNA abrogates apoptosis and growth arrest induction by the NSAID treatment, blocks JNK activation, and restores Cdc2-cyclin B kinase activity. Our results establish MDA-7/IL-24 and GADD45alpha and GADD45gamma as critical mediators of apoptosis and growth arrest in response to NSAIDs in cancer cells. |
| Species | Homo sapiens |
| Quality Metric Scores | nCoCo Score: 879 |
| Information Content | Rich |
| Other IDs | M17956 |
| Base PAG ID | MAX003295 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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