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Implication of c-Myc in apoptosis induced by the retinoid CD437 in human lung carcinoma cells

Oncogene volume 18, pages 3894–3901 (1999)Cite this article

Abstract

The novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) has been recently identified to be a potent inducer of apoptosis in human non-small cell lung carcinoma (NSCLC) cells through a nuclear retinoic acid receptor independent mechanism. To approach the mechanism by which CD437 induces apoptosis in NSCLC cells, we investigated the involvement of c-Myc in CD437-induced apoptosis. CD437 (1 μM) up-regulated the expression of c-Myc and of its downstream target genes ornithine decarboxylase (ODC) and cdc25A in all three NSCLC cell lines (i.e., H460, SK-MES-1 and H1792) used. These effects were correlated with cellular susceptibilities to induction of apoptosis by CD437. Furthermore, CD437-induced apoptosis could be blocked by the ODC inhibitor difluoromethylornithine, the caspase inhibitors Z-VAD FMK and Z-DEVD FMK, and c-Myc antisense oligodeoxynucleotide, respectively. These data indicate that c-Myc gene plays an important role in mediating CD437-induced apoptosis in human NSCLC cells.

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Acknowledgements

WK Hong is an American Cancer Society Clinical Research Professor. This study was supported by United States Public Health Service Grant U19 CA68437 from the National Cancer Institute.

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  1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, Texas, USA

    Shi-Yong Sun, Ping Yue, Waun K Hong & Reuben Lotan

  2. Galderma Research and Development, Sophia Antipolis, France

    Braham Shroot

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Sun, SY., Yue, P., Shroot, B. et al. Implication of c-Myc in apoptosis induced by the retinoid CD437 in human lung carcinoma cells. Oncogene 18, 3894–3901 (1999). https://doi.org/10.1038/sj.onc.1202771

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