Disease relevance of Medullin

• Protective role of p21(Waf1/Cip1) against prostaglandin A2-mediated apoptosis of human colorectal carcinoma cells [1].
• Prostaglandin A2 was much less effective than PGA1 in inhibiting melanoma colony formation [2].
• Assessment of antiviral activity, efficacy, and toxicity of prostaglandin A2 in a rabbit model of herpetic keratitis [3].
• To establish a quantitative assessment of 1 as a chemically stable and orally active prodrug of 2, the hydrolysis of 1 to 2 and the subsequent dehydration of 2 to prostaglandin A2 (3) were followed at 25 degrees C and six pH's ranging from 2.0 to 6.5 by means of a high-pressure liquid chromatographic procedure [4].
• Prostaglandin A2 specifically represses insulin-like growth factor-I gene expression in C6 rat glioma cells [5].

High impact information on Medullin

• Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects [6].
• Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2 [6].
• Prostaglandin A2 (PGA2) treatment induces growth arrest of most cells, and we have recently shown that, for breast carcinoma MCF-7 cells, this is correlated with an induction of the cyclin-dependent kinase inhibitor p21 and reduced cyclin-dependent kinase 2 activity [7].
• We have explored the mechanisms involved in the induction of five stress-response genes (heme oxygenase [HO], c-fos, Egr-1, gadd153, and HSP70) in human diploid fibroblasts growth-arrested by treatment with the antiproliferative prostaglandin A2 (PGA2) [8].
• In contrast, induction of growth arrest by media depletion (starvation) or by treatment with the growth inhibitor prostaglandin A2 did not induce such an increase in mRNA stability in all gadd genes [9].

Chemical compound and disease context of Medullin

• We studied the uptake and metabolism of prostaglandin A2 (PGA2) in mouse L1210 leukemia and L929 fibroblast cell lines in which this prostaglandin has antiviral and antigrowth effects [10].
• Failure of infusion of prostaglandin A2 to restore the response to antidiuretic hormone in rats with polyuria induced by lithium [11].

Biological context of Medullin

• Inhibitory effects of prostaglandin A2 on c-myc expression and cell cycle progression in human leukemia cell line HL-60 [12].
• Prostaglandin A2 (PGA2) reversibly blocked the cell cycle progression of NIH 3T3 cells at G1 and G2/M phase [13].
• Prostaglandin A2 blocks the activation of G1 phase cyclin-dependent kinase without altering mitogen-activated protein kinase stimulation [13].
• This model was confirmed in cells from p21Waf1 knockout mice where PGA2 was completely unable to block the activating phosphorylation of cdk2, or inhibit cdk2 activity [14].
• Treatment of Hela cells with prostaglandin A2 (PGA2) resulted in a marked inhibition of cell proliferation which was associated with a significant induction of gadd153 mRNA, a member of a novel class of genes associated with growth arrest and DNA damage [15].

Anatomical context of Medullin

• The effect of prostaglandin A2 (PGA2) on c-myc expression was investigated in a human promyelocytic leukemia cell line, HL-60, which responded to PGA2 with a dose-dependent growth inhibition [12].
• Prostaglandin A2 (PGA2) inhibited the replication of herpes simplex virus type 1 in rabbit and human cornea stromal cells at concentrations of 1 to 5 microM while causing significant toxicity at 55 to 150 microM [3].
• Interaction of prostaglandin A2 and prostaglandin B2 on vascular smooth muscle tone, vascular reactivity and electrolyte transport [16].
• The effects of prostaglandin A2 (PGA2) and prostaglandin B2 (PGB2) on vascular smooth muscle tone, electrolyte movements and responses to vasoactive stimuli were evaluated with superfused canine tibial arteries [16].
• Effects of prostaglandin A2 on Na+, K+-ATPase activity in basolateral plasma membrane of rat intestine in vitro [17].

Associations of Medullin with other chemical compounds

• The IC50 (concentrations required to inhibit cell growth by 50%) value (0.03 microM (0.01 microgram/ml)) and cytotoxic effects (greater than 0.3 microM (0.1 microgram/ml)) of chlorovulone I were about 200 and 100 times stronger than those of prostaglandin A2, respectively, on the molar basis [18].
• Interactions of prostaglandin A2 with the glutathione-mediated biotransformation system [19].
• Treatment of L1210 cells with prostaglandin A2 (PGA2) or 9-deoxy-delta 9,12-13,14-dihydro PGD2 (delta 12-PGJ2) resulted in significant G2/M arrest and subsequent DNA fragmentation at concentrations that are cytotoxic to the cells [20].
• Blood samples were also collected for the measurement of anti-S-Ag antibody production, thromboxane B2 and prostaglandin A2 levels [21].
• Corticosterone production rate of the decapsulated adrenal gland was not significantly modified by prostaglandin A2 in a concentration effective on the capsular adrenal gland [22].

Gene context of Medullin

• Treatment with the stress agent prostaglandin A2 (PGA2) induces expression of the cyclin-dependent kinase inhibitor p21 [23].
• Identification of cDNAs for Sox-4, an HMG-Box protein, and a novel human homolog of yeast splicing factor SSF-1 differentially regulated during apoptosis induced by prostaglandin A2/delta12-PGJ2 in Hep3B cells [24].
• Prostaglandin A2-mediated stabilization of p21 mRNA through an ERK-dependent pathway requiring the RNA-binding protein HuR [23].
• Prostaglandin A2 acts as a transactivator for NOR1 (NR4A3) within the nuclear receptor superfamily [25].
• Although PGA2 suppresses cyclin D1 and elevates p21Waf1 levels, it was the failure of cdk2 to become activated by phosphorylation which correlated best with growth inhibition [14].

Analytical, diagnostic and therapeutic context of Medullin

• Attempts failed to revert the abnormal wv/wv phenotype in neurons by addition of gangliosides, triiodothyronine T3, prostaglandin A2, medium containing 1% horse serum, conditioned medium from +/+ cerebellar cultures, or by cocultivation with +/+ astrocytes [26].
• Flow cytometry studies showed an increase in S phase and decrease in G1 phase in WHCO3 exposed to PGE2 and PGA2 [27].

References