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Exisulind and CP248 Induce Growth Inhibition and Apoptosis in Human Esophageal Adenocarcinoma and Squamous Carcinoma Cells

Andrew K Joe, Hui Liu, Danhua Xiao, Jae-Won Soh, John T Pinto, David G Beer, Gary A Piazza, W Joseph Thompson, I Bernard Weinstein

J Exp Ther Oncol. Mar-Apr 2003;3(2):83-94.

PMID: 12822514

Abstract:

We examined the effects of exisulind (sulindac sulfone) and a potent derivative CP248 on the Barrett's esophagus (BE)-related adenocarcinoma cell lines Seg-1 and Bic-1, and on HCE7 esophageal squamous carcinoma cells. Marked growth inhibition and apoptosis occurred in all cell lines with IC50 values of 100-300 microM for exisulind and 100 nM for CP248. Bic-1 and HCE7 cells were more sensitive to the growth inhibitory properties of exisulind. Treatment of all cell lines with CP248 for 24 h increased the proportion of cells in mitosis. Exisulind had no effect on cell-cycle progression. Treatment with either compound induced rapid activation of the c-Jun NH2-terminal kinase 1 (JNK1), suggesting that JNK1 activation plays a role in the induction of apoptosis by these compounds. Only Seg-1 cells expressed a detectable basal level of cyclooxygenase-2 (cox-2), providing further evidence that cox-2 is not the critical target for the growth inhibitory and apoptotic effects of these compounds. Cellular levels of reduced glutathione (GSH) increased approximately five-fold in all cell lines after 24 h of treatment with either compound. These studies provide support for the use of exisulind in BE chemoprevention trials, and of exisulind or CP248 in the therapy of patients with esophageal carcinoma.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP49627272 Sulindac Related Compound C Sulindac Related Compound C 49627-27-2 Price
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