Prostaglandin A2 and Δ12‐prostaglandin J2 induce apoptosis in L1210 cells

Kim, In-Kyung; Lee, Jeong-Hwa; Sohn, Hyung Sun; Kim, Ho‐Shik; Kim, Sang-Ho

doi:10.1016/0014-5793(93)80110-g

Cited by 87 publications

(47 citation statements)

References 35 publications

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“…yclopentenone prostaglandins (CyPG) are naturally occurring eicosanoids that display varied biological activities, including antiviral (1) and antitumoral effects (2), modulation of the heat shock response (3), and induction of oxidative stress (4) and apoptosis (5). The CyPG of the J 2 series, such as 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), arise from the spontaneous dehydration of PGD 2 , whereas PGA 2 is produced by PGE 2 dehydration.…”

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confidence: 99%

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

Oliva

Pérez‐Sala²,

Castrillo³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

125

132

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The cyclopentenone 15-deoxy-⌬ 12,14 -prostaglandin J2 (15d-PGJ2) induces cell proliferation and mitogen-activated protein kinase activation. Here, we describe that these effects are mediated by 15d-PGJ 2-elicited H-Ras activation. We demonstrate that this pathway is specific for H-Ras through the formation of a covalent adduct of 15d-PGJ 2 with Cys-184 of H-Ras, but not with N-Ras or K-Ras. Mutation of C184 inhibited H-Ras modification and activation by 15d-PGJ 2, whereas serum-elicited stimulation was not affected. These results describe a mechanism for the activation of the Ras signaling pathway, which results from the chemical modification of H-Ras by formation of a covalent adduct with cyclopentenone prostaglandins.mitogen-activated protein kinase ͉ cell proliferation ͉ posttranslational modification

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mentioning

confidence: 99%

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

Oliva

Pérez‐Sala²,

Castrillo³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

125

132

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“…Cyclopentenone prostaglandins, especially 15-deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ), have been shown to exert antineoplastic effects on various types of human cancer (Kim et al, 1993;Ahn et al, 1998;Clay et al, 1999;Keelan et al, 1999;Butler et al, 2000;Chang and Szabo, 2000;Clay et al, 2001;Straus and Glass, 2001). These effects, frequently attributed to activation of peroxisome proliferator-activated receptor gamma (PPARg), have been recently proven to be at least partially mediated through PPARg-independent pathways (Clay et al, 2001(Clay et al, , 2002Straus and Glass, 2001;Hsiang and Straus, 2002;Liu et al, 2003).…”

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confidence: 99%

Abrogation of IL-6-mediated JAK signalling by the cyclopentenone prostaglandin 15d-PGJ2 in oral squamous carcinoma cells

2004

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Cyclopentenone 15-deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ) exerts antineoplastic effects on various types of human cancer. We recently showed that treatment with 15d-PGJ 2 induces apoptosis accompanied by downregulation of the oncogenic signal transducer and activator of transcription 3 (Stat3) signalling in human oral squamous cell carcinoma (SCC) cells. The current study examines the effects of 15d-PGJ 2 on the epidermal growth factor receptor (EGFR) and Janus Kinase (JAK)-mediated signalling pathways. Inhibition of Stat3 by 15d-PGJ 2 was abolished by exogenous stimulation with transforming growth factor alpha (TGF-a), but not interleukin 6 (IL-6), supporting a selective effect of 15d-PGJ 2 on IL-6-mediated signalling. Importantly, 15d-PGJ 2 selectively abrogated constitutive and IL-6-mediated JAK phosphorylation without affecting EGFR-activated levels. Moreover, the inhibitory effect of 15d-PGJ 2 on JAK signalling required the reactive a,b-unsaturated carbon within the cyclopentenone ring. Targeting of JAK signalling using a specific JAK inhibitor also abolished Stat3 phosphorylation and resulted in apoptosis in oral SCC cells. Our findings provide the first evidence for 15d-PGJ 2 -mediated downregulation of constitutive and IL-6-induced JAK signalling in cancer and support that JAK inhibition and suppression of EGFR-independent Stat3 activation by 15d-PGJ 2 represent a promising approach for induction of apoptosis in oral SCC cells.

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“…Thus, cyclin D1 expression and S-phase entry were induced by prostaglandin F2α in Swiss 3T3 fibroblasts, whereas other prostaglandins were able to arrest cells at the G2/M phase of the cell cycle. 49,50 We have shown that cPLA 2 activity increased transiently during mid-G1 phase of the ongoing cell cycle of CHO and neuroblastoma N2A cells, this activity being dependent upon the activity of p42/44. 51,52 By using different inhibitors of cPLA 2 , it was demonstrated that the activity of cPLA 2 in mid-G1 phase was required for entry into S phase.…”

Section: A the Map Kinase Pathwaymentioning

confidence: 95%

Signal Transduction and Actin in the Regulation of G1-Phase Progression

Boonstra

Moes

2005

Crit Rev Eukar Gene Expr

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Regulation of cell proliferation is dependent on the integration of signal transduction systems that are activated by external signal molecules, such as growth factors and extracellular matrix components. Dependent on these signal transduction networks, the cells decide in the G1 phase to continue proliferation or, alternatively, to stop cell-cycle progression and undergo apoptosis, differentiation, or quiescence. The MAP kinase and PI-3 kinase pathways have been demonstrated to play an essential role in these G1-phase decisions. Interestingly, actin has been demonstrated to mutually interfere with signal transduction. In addition, it has been indicated that the FOXO transcription factors are involved in these decisions, as well. Actin has been demonstrated to play an important role in the regulation of G1-phase progression. Because of its properties as a structural protein, actin is essential in cytokinesis and in cell spreading and, thus, is involved in G1-phase progression. As an intermediate factor in signal transduction, actin is likely to be involved in cell-cycle regulation induced by external signal molecules. And, finally, actin has been demonstrated to play a direct role in transcription. These observations indicate a prominent role of actin in the regulation of G1-phase progression.

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Prostaglandin A₂ and Δ¹²‐prostaglandin J₂ induce apoptosis in L1210 cells

Cited by 87 publications

References 35 publications

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

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

Abrogation of IL-6-mediated JAK signalling by the cyclopentenone prostaglandin 15d-PGJ2 in oral squamous carcinoma cells

Signal Transduction and Actin in the Regulation of G1-Phase Progression

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Prostaglandin A2 and Δ12‐prostaglandin J2 induce apoptosis in L1210 cells

Cited by 87 publications

References 35 publications

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

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

Abrogation of IL-6-mediated JAK signalling by the cyclopentenone prostaglandin 15d-PGJ2 in oral squamous carcinoma cells

Signal Transduction and Actin in the Regulation of G1-Phase Progression

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Product

Resources

About

Prostaglandin A₂ and Δ¹²‐prostaglandin J₂ induce apoptosis in L1210 cells

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

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