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Pentoxifylline Augments but Does Not Antagonize TNFα-Mediated Neuroblastoma Cell Differentiation: Modulation of Calcium Mobilization but Not cAMP

Authors
Journal
Biochemical and Biophysical Research Communications
0006-291X
Publisher
Elsevier
Publication Date
Volume
211
Issue
3
Identifiers
DOI: 10.1006/bbrc.1995.1911

Abstract

Abstract We described here that pentoxifylline (PTX), which is well known to counteract tumor necrosis factor alpha (TNFα)-mediated inflammatory responses, augmented TNFα-induced neuroblastoma cell differentiation in conjunction with growth inhibition and cell-cycle arrest in G1 phase. PTX also enhanced TNFα-induced down-regulation of acetylcholine-mediated [Ca 2+] i mobilization in neuroblastoma cells. Furthermore, we found that addition of cAMP failed to induce neuroblastoma cell differentiation, whereas blockade of [Ca 2+] i mobilization by 8-(N,N-diethyl-amino)octyl-3,4,5-trimethoxybenzoate HCl (TMB-8, 10 μM) did induce neuroblastoma cell differentiation. Taken together, these results indicated that PTX possessed a novel signal transduction, down-regulation of [Ca 2+] i mobilization, to augment but not counteract TNFα-mediated functions.

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