Alterations of MCF-7 Human Breast Cancer Cell after Prostaglandins PGA₁ and PGF_2α‘Treatment

Abstract

Treatment of monolayer cultures of MCF-7 cells with prostaglandins PGA₁and PGF_2α inhibited cell proliferation, reduced the rate of labeled precursor incorporation into DNA, RNA, and protein, and induced morphological changes in a dose-dependent manner. The rate of [³H]thymidine incorporation was increased by PGA₁ at l0^–10–l0^–8M, while a sharp decrease was observed at 10^–6–10^–4 M(p < 0.05 and p < 0.005). PGF_2α inhibited [³H]thymidine incorporation at all concentrations tested. Similar results were obtained for [³H]uridine incorporation with both PGs. PGA₁ inhibited [³H]leucine incorporation at 10^–4M, but increased incorportion at 10^–10–10^–6M. At the ultrastructural level, neither PG induced morphological alterations at 10^–12–10^–8M. However, at 10^–6–10^–4 Mboth PGA₁ and PGF_2α diminished the number and size of cell surface projections; some cells appeared to completely lack microvilli. Disorganization of mitochondrial cristae and increased electron density of the matrix were also evident

Alkylation of the Tumor Suppressor PTEN Activates Akt and β-Catenin Signaling: A Mechanism Linking Inflammation and Oxidative Stress with Cancer

“…Akt kinase activation also coincided with Akt-dependent proliferation in MCF-7 cells treated with 1–10 µM Δ12-PGJ 2 ( Figure 4B ) . This finding is consistent with reported bi-phasic actions of cyPGs, whereby they increase proliferation of cultured cells at ∼1 µM [37] , [38] , while they decrease proliferation or cause apoptosis by modifying other protein targets at ∼50 µM [39] .…”

Formation of Reactive Cyclopentenone Compounds in Vivo as Products of the Isoprostane Pathway

“…These cytostatic effects can be reversible, but higher concentrations are cytotoxic and induce apoptosis (4,6,7). Interestingly, at very low concentrations, PGA was found to stimulate cellular proliferation (8). CP-PGs can also activate nuclear peroxisome proliferator-activated receptor-␥ and suppress macrophage activation and inflammatory responses (9 -11).…”

The cyclopentenone 15-deoxy-Δ 12,14 -prostaglandin J 2 binds to and activates H-Ras

“…However, the nature of their effect appears to be cell type-and dose-dependent. Although antiproliferative or proapoptotic effects have been most frequently described (14), CyPG have also been found to induce cell proliferation in mesangial (15), breast cancer (16), and COX-2-depleted colorectal cancer cells (13) when used at nanomolar or low micromolar concentrations. It has been reported that 15d-PGJ 2 can cause the activation of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) 1͞2 (17)(18)(19), and that phosphatidylinositol 3-kinase (PI3-kinase) inhibitors reduce 15d-PGJ 2 -elicited cell proliferation (15).…”