Synthetic retinoid CD437 induces apoptosis of esophageal squamous HET-1A cells through the caspase-3-dependent pathway

6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD4 37) is a novel retinoid that has shown to be a potent inducer of apoptosis in cancer cells. We investigated the apoptosis-inducing activity of CD437 a nd its mechanism of action in the human esophageal squamous epithelial cell line (HET-IA). CD437 decreased HET-1A cell viability in a time and dose de pendent manner. CD437 was found to induce DNA fragmentation. Apoptosis was accompanied by markedly increased activity of caspase-3 as well expression of caspase-3 and -8 and APRP fragmentation. The CD437-mediated activation o f caspase-3 was inhibited by Z-DEVD-FMK These data indicate that CD437-indu ced apoptosis in HET-1A cells may be mediated through the caspase-3 depende nt pathway. In addition, apoptosis was also accompanied by increased expres sion of Bad protein and downregulation of Bcl-2 expression. Phosphorylation of Jun occurred following CD437 exposure indicating that Jun kinase (JNK) activity was strongly induced by CD437 Understanding these apoptotic pathwa ys of esophageal epithelial cells may allow therapeutic induction of cell d eath in malignant or premalignant lesions of the esophagus by agents such a s CD437.