ArticleProceedings of the National Academy of Sciences of the United States of America2002
mda-7 (IL-24) Mediates selective apoptosis in human melanoma cells by inducing the coordinated overexpression of the GADD family of genes by means of p38 MAPK.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 1 of them a synthesis that pooled it.
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132 citing papers in PubMed, 1 synthesis or guideline pooled it, 306 citations in OpenAlex.
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- Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases.International journal of molecular sciences · 2022Review
- Strategies for Improving Photodynamic Therapy Through Pharmacological Modulation of the Immediate Early Stress Response.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Induction ofScience signaling · 2021Article
- Role of IL-24 in NK cell activation and its clinical implication in systemic lupus erythematosus.Clinical rheumatology · 2021Article
- Interleukin-24 regulates mucosal remodeling in inflammatory bowel diseases.Journal of translational medicine · 2021Article
- Nogo-A-Δ20/EphA4 interaction antagonizes apoptosis of neural stem cells by integrating p38 and JNK MAPK signaling.Journal of molecular histology · 2021Article
- Therapeutic wavelengths of ultraviolet B radiation activate apoptotic, circadian rhythm, redox signalling and key canonical pathways in psoriatic epidermis.Redox biology · 2021Article
- IL-24-Armed Oncolytic Vaccinia Virus Exerts Potent Antitumor Effects via Multiple Pathways in Colorectal Cancer.Oncology research · 2021Article
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72 more citing papers are in PubMed but not listed here.
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8 authors at 2 institutions in 1 country.
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Abstract
Subtraction hybridization identified melanoma differentiation-associated gene-7 (mda-7) as a gene induced during terminal differentiation in human melanoma cells. On the basis of structure, chromosomal localization and cytokine-like properties, mda-7 is classified as IL-24. Administration of mda-7/IL-24 by means of a replication-incompetent adenovirus (Ad.mda-7) induces apoptosis selectively in diverse human cancer cells without inducing harmful effects in normal fibroblast or epithelial cells. The present studies investigated the mechanism underlying this differential apoptotic effect. Infection of melanoma cells, but not normal immortal melanocytes, with Ad.mda-7 induced a time- and dose-dependent increase in expression, mRNA and protein, of a family of growth arrest and DNA damage (GADD)-inducible genes, which correlated with induction of apoptosis. Among the members of the GADD family of genes, GADD153, GADD45 alpha, and GADD34 displayed marked, and GADD45 gamma showed minimal induction. Treatment of melanoma cells with SB203580, a selective inhibitor of the p38 mitogen-activated protein kinase (MAPK) pathway, effectively inhibited Ad.mda-7-induced apoptosis. Additional support for an involvement of the p38 MAPK pathway in Ad.mda-7-mediated apoptosis was documented by using an adenovirus expressing a dominant negative mutant of p38 MAPK. Infection with Ad.mda-7 increased the phosphorylation of p38 MAPK and heat shock protein 27 in melanoma cells but not in normal immortal melanocytes. In addition, SB203580 effectively inhibited Ad.mda-7-mediated induction of the GADD family of genes in a time- and dose-dependent manner, and it effectively blocked Ad.mda-7-mediated down-regulation of the antiapoptotic protein BCL-2. Inhibition of GADD genes by an antisense approach either alone or in combination also effectively blocked Ad.mda-7-induced apoptosis in melanoma cells. These results support the hypothesis that Ad.mda-7 mediates induction of the GADD family of genes by means of the p38 MAPK pathway, thereby resulting in the selective induction of apoptosis in human melanoma cells.
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