1998
DOI: 10.1074/jbc.273.29.18522
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Potent Prostaglandin A1 Analogs That Suppress Tumor Cell Growth through Induction of p21 and Reduction of Cyclin E

Abstract: Although the cyclopentenone prostaglandin A 1 (PGA 1 ) is known to arrest the cell cycle at the G 1 phase in vitro and to suppress tumor growth in vivo, its relatively weak activity limits its usefulness in cancer chemotherapy. In an attempt to develop antitumor drugs of greater potency and conspicuous biological specificity, we synthesized novel analogs based on the structure of PGA 1 . Of the newly synthesized analogs, 15-epi-⌬ 7 -PGA 1 methyl ester (NAG-0092), 12-iso-⌬ 7 -PGA 1 methyl ester (NAG-0093), and … Show more

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Cited by 52 publications
(34 citation statements)
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“…[18][19][20] Our observations that the effects of PGA 2 ; induction of p21 Cip1 , suppression of cyclin D1, and inducibility of cell death, were enhanced in spleen cells derived from NOR1-overexpressing transgenic mice, suggest that the effects of PGA 2 are influenced, at least in part, by the expression levels of NOR1.…”
Section: Discussionmentioning
confidence: 87%
See 1 more Smart Citation
“…[18][19][20] Our observations that the effects of PGA 2 ; induction of p21 Cip1 , suppression of cyclin D1, and inducibility of cell death, were enhanced in spleen cells derived from NOR1-overexpressing transgenic mice, suggest that the effects of PGA 2 are influenced, at least in part, by the expression levels of NOR1.…”
Section: Discussionmentioning
confidence: 87%
“…[18][19][20] To clarify whether the effects of PGA 2 are influenced by the expression levels of NOR1, we investigated the effects of PGA 2 on spleen cells derived from the NOR1 transgenic mice. We generated the NOR1 transgenic mice, into which 10 copies of the actin promoter-constructed NOR1 gene had been incorporated.…”
Section: Screening Of Transactivators For Nor1 Nuclear Receptor By Mamentioning
confidence: 99%
“…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).…”
mentioning
confidence: 99%
“…This appears to be associated with the finding that all of the cyclin E-Cdk2 complex, but only a minor portion of the cyclin A-Cdk2 complex, was already associated with p21 before treatment with IL-1. Such a physical association of p21 with active cyclin E-Cdk2 but not with cyclin ACdk2 in growing cells is also observed in normal human fibroblasts (37) and in certain cell lines (51,52). These observations suggest that at least in these cells and cell lines, p21 binds to cyclin E-Cdk2 complex with much higher affinity than to cyclin A-Cdk2 complex, and thus p21 is a more effective inhibitor of cyclin E-Cdk2 than of cyclin A-Cdk2 in vivo.…”
Section: Discussionmentioning
confidence: 86%