The modulation effect of vitamin E on prostaglandin E2 level and ornithine decarboxylase activity at the promotion phase of lung tumorigenesis in mice

Yano, Tomohiro; Yano, Yoshihisa; Uchida, Mikako; Murakami, Ayumi; Hagiwara, Kiyokazu; Otani, Shuzo; Ichikawa, Tomio

doi:10.1016/s0006-2952(96)00869-6

Cited by 12 publications

(18 citation statements)

References 13 publications

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“…In previous reports, indomethacin has been shown to exert a chemopreventive action by affecting polyamine metabolism in colon cancers, and reduced intracellular polyamine contents led to the induction of apoptosis [24,25]. We have also reported that indomethacin suppresses the elevation of polyamine at the promotion stage of lung tumorigenesis in mice [26,27]. Furthermore, it has been reported that the activation of PPARd can induce the transcriptional activation of SSAT, a key polyamine catabolic enzyme [28].…”

Section: Resultsmentioning

confidence: 81%

Peroxisome proliferator‐activated receptor δ as a molecular target to regulate lung cancer cell growth

et al. 2005

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It has been assumed that prostaglandin (PG)I 2 signaling contributes to the negative growth control of lung cancer cells; however, the mechanism remains unresolved. PGI 2 functions through a cell surface G protein-coupled receptor (prostaglandin I2-binding receptor, IP) and also exerts an effect by interacting with a nuclear hormone receptor, peroxisome proliferator-activated receptor d (PPARd). We found that PPARd was a key molecule of PGI 2 signaling to give negative growth control of lung cancer cells (A549), using carbarprostacyclin, a PGI 2 agonist for IP and PPARd, and L-165041, a PPARd agonist. Furthermore, PPARd-induced cell growth control was reinforced by the inhibition of cyclooxygenase. These results suggest that PPARd activation under the suppression of PG synthesis is important to regulate lung cancer cell growth.

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Section: Resultsmentioning

confidence: 81%

Peroxisome proliferator‐activated receptor δ as a molecular target to regulate lung cancer cell growth

et al. 2005

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“…We focused on EP 3 receptors that are most ubiquitous of the four EP subtypes (6) and also examined localization of EP 4 receptors. Our data provide novel evidence for the existence of EP 3 and EP 4 receptors in the nuclear envelope and reveal that these receptors are functional, and their actions appear to involve pertussis toxin (PTX)-sensitive G proteins. Animals-Newborn pigs (1-3 days old) were killed with intracardiac pentobarbital under halothane anesthesia, and tissues of interest were removed.…”

mentioning

confidence: 77%

“…Altogether these data raise the possibility of the presence of nuclear prostanoid receptors. This inference has recently been suggested for EP 1 (19), but whether or not this single observation is specific for this receptor or applies to other prostanoid receptors, especially of the widely distributed EP 3 and EP 4 subtypes, is unknown.…”

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confidence: 94%

Localization of Functional Prostaglandin E2 Receptors EP3 and EP4 in the Nuclear Envelope

Bhattacharya

Peri

Ribeiro‐da‐Silva

et al. 1999

Journal of Biological Chemistry

211

159

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The effects of prostaglandin E 2 are thought to be mediated via G protein-coupled plasma membrane receptors, termed EP. However recent data implied that prostanoids may also act intracellularly. We investigated if the ubiquitous EP 3 and the EP 4 receptors are localized in nuclear membranes. Radioligand binding studies on isolated nuclear membrane fractions of neonatal porcine brain and adult rat liver revealed the presence of EP 3 and EP 4 . A perinuclear localization of EP 3␣ and EP 4 receptors was visualized by indirect immunocytofluorescence and confocal microscopy in porcine cerebral microvascular endothelial cells and in transfected HEK 293 cells that stably overexpress these receptors. Immunoelectron microscopy clearly revealed EP 3␣ and EP 4 receptors localization in the nuclear envelope of endothelial cells; this is the first demonstration of the nuclear localization of these receptors. Data also reveal that nuclear EP receptors are functional as they affect transcription of genes such as inducible nitric-oxide synthase and intranuclear calcium transients; this appears to involve pertussis toxin-sensitive G proteins. These results define a possible molecular mechanism of action of nuclear EP 3 receptors.Prostaglandin E 2 (PGE 2 ) 1 is one of the most abundant prostanoids in the brain (1) and plays an important role in many cerebral functions, particularly in the newborn (2). PGE 2 also influences mitogenesis (3), promotes growth and metastasis of tumors (4), and stimulates gene transcription (5). To date, the biological actions of PGE 2 have been attributed to result from its interaction with plasma membrane G protein-coupled receptors termed EP, which include EP 1 , EP 2 , EP 3 , and EP 4 subtypes (6). Recent studies have shown that the nuclear membrane contains high levels of cyclooxygenase-1 and -2 and of PGE 2 (7). Possible intracellular sites of action for prostanoids are also suggested by other data. For example, a transporter that mediates the influx of prostanoid has been identified (8). Cytosolic phospholipase A 2 undergoes a calcium-dependent translocation to the nuclear envelope (9), and cyclooxygenase-2 has been shown to translocate to the nucleus in response to certain growth factors (10). It is thus possible that prostanoids may exert some of their effects via intracellular EP receptors, to have a direct nuclear action as recently proposed by Goetzl et al. (11), and Morita et al. (12).It has generally been assumed that the signal transduction cascades are initiated at the plasma membrane and not the nuclear membranes. However, recent studies have disclosed that the nuclear envelope plays a major role in signal transduction cascades (13,14). In fact, a novel nuclear lipid metabolism that is a part of unique nuclear signaling cascade termed NEST (nuclear envelope signal transduction) has been hypothesized (15). Both heterotrimeric and low molecular weight G proteins (15, 16), phospholipase C (13), phospholipase D (15), and adenylate cyclase (17) have shown to be localized at the nucleus. Th...

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“…PGE2 is a major product of COX and regulates wound repair (Joyce et al, 1994), cell migration (Joyce et al, 1995), and angiogenesis (BenEzra, 1978;Form et al, 1983). PGE2 also mediates mitogenesis (Baylink et al, 1996), growth and metastasis of tumors (Yano et al, 1997), and gene transcription (Simonson et al, 1994). These biological actions of PGE2 are mediated through ligation of four distinct G protein-coupled receptors [E-prostanoid (EP)1, EP2, EP3, and EP4] (Breyer et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 stimulates angiogenesis by activating the nitric oxide/cGMP pathway in human umbilical vein endothelial cells

Namkoong

Lee²,

Kim³

et al. 2005

Exp Mol Med

116

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Prostaglandin E 2 (PGE 2 ), a major product of cyclooxygenase, has been implicated in modulating angiogenesis, vascular function, and inflammatory processes, but the underlying mechanism is not clearly elucidated. We here investigated the molecular mechanism by which PGE2 regulates angiogenesis. Treatment of human umbilical vein endothelial cells (HUVEC) with PGE 2 increased angiogenesis. PGE 2 increased phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), eNOS activity, and nitric oxide (NO) production by the activation of cAMP-dependent protein kinase (PKA) and phosphatidylinositol 3-kinase (PI3K). Dibutyryl cAMP (DB-cAMP) mimicked the role of PGE 2 in angiogenesis and the signaling pathway, suggesting that cAMP is a down-stream mediator of PGE2. Furthermore, PGE2 increased endothelial cell sprouting from normal murine aortic segments, but not from eNOS-deficient ones, on Matrigel. The angiogenic effects of PGE 2 were inhibited by the inhibitors of PKA, PI3K, eNOS, and soluble guanylate cyclase, but not by phospholipase C inhibitor. These results clearly show that PGE2 increased angiogenesis by activating the NO/cGMP signaling pathway through PKA/PI3K/Akt-dependent increase in eNOS activity.

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The modulation effect of vitamin E on prostaglandin E2 level and ornithine decarboxylase activity at the promotion phase of lung tumorigenesis in mice

Cited by 12 publications

References 13 publications

Peroxisome proliferator‐activated receptor δ as a molecular target to regulate lung cancer cell growth

Peroxisome proliferator‐activated receptor δ as a molecular target to regulate lung cancer cell growth

Localization of Functional Prostaglandin E2 Receptors EP3 and EP4 in the Nuclear Envelope

Prostaglandin E2 stimulates angiogenesis by activating the nitric oxide/cGMP pathway in human umbilical vein endothelial cells

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