Systematic name M17956
Brief description 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].
Full description or abstract 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17178890   Authors: Zerbini LF,Czibere A,Wang Y,Correa RG,Otu H,Joseph M,Takayasu Y,Silver M,Gu X,Ruchusatsawat K,Li L,Sarkar D,Zhou JR,Fisher PB,Libermann TA
Exact source Table 1S: FC < 0
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