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

X. Wan, M. D. Duncan, P. Nass, J. W. Harmon

Research output: Contribution to journalArticle

Abstract

6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) 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 and its mechanism of action in the human esophageal squamous epithelial cell line (HET-1A). CD437 decreased HET-1A cell viability in a time and dose dependent 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 of caspase-3 was inhibited by Z-DEVD-FMK. These data indicate that CD437-induced apoptosis in HET-1A cells may be mediated through the caspase-3 dependent pathway. In addition, apoptosis was also accompanied by increased expression 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 pathways of esophageal epithelial cells may allow therapeutic induction of cell death in malignant or premalignant lesions of the esophagus by agents such as CD437.

Original languageEnglish (US)
Pages (from-to)2657-2663
Number of pages7
JournalAnticancer Research
Volume21
Issue number4 A
StatePublished - Nov 24 2001

Keywords

  • Apoptosis
  • CD437
  • Caspase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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