Acetylsalicylic acid (ASA) protects the prostaglandin-cAMP-system of human hypernephroma cells against irradiation-induced alterations

Abstract

Summary There is abundant evidence that inhibitors of prostaglandin (PG) 3.6nM; PGI2: Bmax = 325 ± 194 fmol mg-protein, Kd = 6.8 ± 7.1nM) were significantly (P < 0.01) diminished.However, irradiation had no significant effect on PG bindig sites in ASA-pretreated cells (PGEI:Bmax =699 ± 240fmolmg-protein, Kd = 3.5 + 1.8nM; iloprost: Bmax = 766 ± 452 fmol mg-' protein, Kd = 3.2 ± 2.2nM). Although there was no significant difference in the basal values for cAMP between control and ASA-treated group cells, the PG-induced cAMP-production was less pronounced in the control group.Taken together, the findings suggest that ASA may modify the radioresponse of cultured human hypernephroma cells by preventing the decrease of PG binding sites induced by irradiation.

Proteinase-Activated Receptor-2 Stimulates Prostaglandin Production in Keratinocytes: Analysis of Prostaglandin Receptors on Human Melanocytes and Effects of PGE2 and PGF2α on Melanocyte Dendricity

“…Phorbol esters were included in the media to support viability. Previous studies have shown that endogenously produced PG may downregulate EP receptors (Hashimoto et al, 1991;Li et al, 1993) which could diminish the effect of exogenous PG on dendricity. We therefore first assessed the endogenous production of PGE 2 and PGF 2a in human melanocytes grown in growth factor depleted medium.…”

Characterization of123I-vascular endothelial growth factor-binding sites expressed on human tumour cells: Possible implication for tumour scintigraphy

“…11,14 In initial experiments, the time course of association of binding was studied by incubating intact cells ( 121 or increasing concentrations (0.001-1000 nM) of other peptides (VIP, SST-14, TNF-␣, EGF and IGF-I). After incubation, the reaction mixture was diluted 1:10 with assay buffer (4°C) and rapidly centrifuged (5,000 g, 10 min, 4°C) to separate membrane-bound from free ligand.…”

Loss of the EP2 Prostaglandin E2 Receptor in Immortalized Human Keratinocytes Results in Increased Invasiveness and Decreased Paxillin Expression

“…Previous reports have suggested that loss of prostaglandin E receptor radioligand-binding activity is associated with more advanced malignancy. 33,[35][36][37] Moreover, treatment of metastatic murine mammary tumor cells with PGE 2 receptor antagonists leads to decreased PGE 2induced cAMP production and increased lung metastasis. 47 We demonstrate that loss of EP 2 receptors in an immortalized, but nontumorigenic human keratinocyte cell line (HaCat) results in increased invasiveness in an organ culture model.…”

“…30 -34 Several reports have demonstrated decreased radiolabeled PGE 2 -binding sites by Scatchard analysis in human and rat breast cancer cell lines and hepatocellular carcinoma. [35][36][37] This decreased receptor binding activity led Li and colleagues 33 to propose that the increased prostaglandin production in malignancy might result in prostaglandin receptor down-regulation. Thus, ligand-dependent receptor down-regulation might represent a possible mechanism for the effects of PGE 2 in malignant progression.…”