Pentoxifylline augments but does not antagonize TNF alpha-mediated neuroblastoma cell differentiation: modulation of calcium mobilization but not cAMP.
We described here that pentoxifylline (PTX), which is well known to counteract tumor necrosis factor alpha (TNF alpha)-mediated inflammatory responses, augmented TNF alpha-induced neuroblastoma cell differentiation in conjunction with growth inhibition and cell-cycle arrest in G1 phase. PTX also enhanced TNF alpha-induced down-regulation of acetylcholine-mediated [Ca2+]i mobilization in neuroblastoma cells. Furthermore, we found that addition of cAMP failed to induce neuroblastoma cell differentiation, whereas blockade of [Ca2+]i mobilization by 8-(N,N-diethyl-amino)octyl-3,4,5-trimethoxybenzoate HCl (TMB-8, 10 microM) did induce neuroblastoma cell differentiation. Taken together, these results indicated that PTX possessed a novel signal transduction, down-regulation of [Ca2+]i mobilization, to augment but not counteract TNF alpha-mediated functions.
Yang
K D
KD
Department of Pediatrics, Tri-service General Hospital, Taipei, Taiwan, R.O.C.
Chuen
H L
HL
Shaio
M F
MF
D000109:Acetylcholine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation; D004357:Drug Synergism; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014409:Tumor Necrosis Factor-alpha; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D000242:Cyclic AMP; D000109:Acetylcholine; D010431:Pentoxifylline; D002118:Calcium