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| Item Type: | Article |
|---|---|
| Title: | Treatment of melanoma cells with the synthetic retinoid CD437 induces apoptosis via activation of AP-1 in vitro, and causes growth inhibition in xenografts in vivo |
| Creators Name: | Schadendorf, D., Kern, M.A., Artuc, M., Pahl, H.L., Rosenbach, T., Fichtner, I., Nuernberg, W., Stueting, S., von Stebut, E., Worm, M., Makki, A., Jurgovsky, K., Kolde, G. and Henz, B.M. |
| Abstract: | Human malignant melanoma is notoriously resistant to pharmacological modulation. We describe here for the first time that the synthetic retinoid CD437 has a strong dose-dependent antiproliferative effect on human melanoma cells (IC50: 5 x 10(-6) M) via the induction of programmed cell death, as judged by analysis of cell morphology, electron microscopical features, and DNA fragmentation. Programmed cell death was preceded by a strong activation of the AP-1 complex in CD437-treated cells as demonstrated by gel retardation and chloramphenicol transferase (CAT) assays. Northern blot analysis showed a time-dependent increase in the expression of c-fos and c-jun encoding components of AP-1, whereas bcl-2 and p53 mRNA levels remained constant. CD437 also exhibited a strong growth inhibitory effect on MeWo melanoma cells in a xenograft model. In tissue sections of CD437-treated MeWo tumors from these animals, apoptotic melanoma cells and c-fos overexpressing cells were colocalized by TdT-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) staining and in situ hybridization. Taken together, this report identifies CD437 as a retinoid that activates and upregulates the transcription factor AP-1, leading eventually to programmed cell death of exposed human melanoma cells in vitro and in vivo. Further studies are needed to evaluate whether synthetic retinoids such as CD437 represent a new class of retinoids, which may open up new ways to a more effective therapy of malignant melanoma. |
| Keywords: | Apoptosis, Chloramphenicol O-Acetyltransferase, Cultured Tumor Cells, DNA Fragmentation, Electron Microscopy, Growth Inhibitors, Heterologous Transplantation, Melanoma, Messenger RNA, Neoplasm Transplantation, Northern Blotting, Retinoids, Transcription Factor AP-1, Transfection, Animals, Mice |
| Source: | Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Volume: | 135 |
| Number: | 6 Pt 2 |
| Page Range: | 1889-1898 |
| Date: | December 1996 |
| Additional Information: | Copyright (c) 1996 by The Rockefeller University Press |
| Official Publication: | https://doi.org/10.1083/jcb.135.6.1889 |
| PubMed: | View item in PubMed |
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