Prostaglandin E2 Protects Gastric Mucosal Cells from Apoptosis via EP2 and EP4 Receptor Activation

Hoshino, Tatsuya; Tsutsumi, Shinji; Tomisato, Wataru; Hwang, Han-Jeong; Tsuchiya, Tomofusa; Mizushima, Tohru

doi:10.1074/jbc.m212097200

Cited by 135 publications

(102 citation statements)

References 45 publications

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“…Akt and PKA activation can mediate prosurvival pathways through the inactivation of proapoptotic proteins (34,35). Our results are consistent with the report that PGE 2 protected gastric mucosal cells in vitro from ethanol-induced apoptosis via EP1 and EP4 activation (36). The inhibitory effect of GSPs on lung cancer cell proliferation through the inhibitory effect on EP1 or EP4 was further confirmed by treating the cells with EP4 agonist.…”

Section: Discussionsupporting

confidence: 92%

Proanthocyanidins Inhibit In vitro and In vivo Growth of Human Non–Small Cell Lung Cancer Cells by Inhibiting the Prostaglandin E2 and Prostaglandin E2 Receptors

Sharma

Meeran

Katiyar

2010

Molecular Cancer Therapeutics

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Overexpression of cyclooxygenase-2 (COX-2) and prostaglandins (PG) is linked to a wide variety of human cancers. Here, we assessed whether the chemotherapeutic effect of grape seed proanthocyanidins (GSP) on non-small cell lung cancer (NSCLC) cells is mediated through the inhibition of COX-2 and PGE 2 /PGE 2 receptor expression. The effects of GSPs on human NSCLC cell lines in terms of proliferation, apoptosis, and expression of COX-2, PGE 2 , and PGE 2 receptors were determined using Western blotting, fluorescence-activated cell sorting analysis, and reverse transcription-PCR. In vitro treatment of NSCLC cells (A549, H1299, H460, H226, and H157) with GSPs resulted in significant growth inhibition and induction of apoptosis, which were associated with the inhibitory effects of GSPs on the overexpression of COX-2, PGE 2 , and PGE 2 receptors (EP1 and EP4) in these cells. Treatment of cells with indomethacin, a pan-COX inhibitor, or transient transfection of cells with COX-2 small interfering RNA, also inhibited cell growth and induced cell death. The effects of a GSP-supplemented AIN76A control diet fed to nude mice bearing tumor xenografts on the expression of COX-2, PGE 2 , and PGE 2 receptors in the xenografts were also evaluated. The growth-inhibitory effect of dietary GSPs (0.5%, w/w) on the NSCLC xenograft tumors was associated with the inhibition of COX-2, PGE 2 , and PGE 2 receptors (EP1, EP3, and EP4) in tumors. This preclinical study provides evidence that the chemotherapeutic effect of GSPs on lung cancer cells in vitro and in vivo is mediated, at least in part, through the inhibition of COX-2 expression and subsequently the inhibition of PGE 2 and PGE 2 receptors.Mol Cancer Ther; 9(3); 569-80. ©2010 AACR.

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Section: Discussionsupporting

confidence: 92%

Proanthocyanidins Inhibit In vitro and In vivo Growth of Human Non–Small Cell Lung Cancer Cells by Inhibiting the Prostaglandin E2 and Prostaglandin E2 Receptors

Sharma

Meeran

Katiyar

2010

Molecular Cancer Therapeutics

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“…PGE 2 inhibits apoptosis in gastric mucosa cells via the mitochondrial pathway and PKA activation. 40 In cholangiocarcinoma cells, celecoxib suppressed Akt phosphorylation and favored the execution of apoptosis. 19 Few reports describe the direct effect of COX-2 expression on apoptosis in liver or HCC cells.…”

Section: Discussionmentioning

confidence: 99%

Protection against Fas-induced liver apoptosis in transgenic mice expressing cyclooxygenase 2 in hepatocytes

et al. 2007

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Cyclooxygenase-2 (COX-2) is upregulated in many cancers, and the prostanoids synthesized increase proliferation, improve angiogenesis, and inhibit apoptosis in several tissues. To explore the function of COX-2 in liver, transgenic (Tg) mice were generated containing a fusion gene (LIVhCOX-2) consisting of human COX-2 cDNA under the control of the human ApoE promoter. Six lines were developed; all of them expressed the LIVhCOX-2 transgene selectively in hepatocytes. The Tg mice exhibited a normal phenotype, and the increased levels of PGE 2 found were due to the constitutively expressed COX-2. Histological analysis of different tissues and macroscopic examination of the liver showed no differences between wild-type (Wt) and Tg animals.

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“…Immunoblotting Analysis-Whole cell extracts were prepared as described previously (32). The protein concentration of each sample was determined by the Bradford method (31).…”

Section: Methodsmentioning

confidence: 99%

Prevention of UVB Radiation-induced Epidermal Damage by Expression of Heat Shock Protein 70

Matsuda

Hoshino

Yamashita

et al. 2010

Journal of Biological Chemistry

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Irradiation with UV light, especially UVB, causes epidermal damage via the induction of apoptosis, inflammatory responses, and DNA damage. Various stressors, including UV light, induce heat shock proteins (HSPs) and the induction, particularly that of HSP70, provides cellular resistance to such stressors. The anti-inflammatory activity of HSP70, such as its inhibition of nuclear factor kappa B (NF-B), was recently revealed. These in vitro results suggest that HSP70 protects against UVB-induced epidermal damage. Here we tested this idea by using transgenic mice expressing HSP70 and cultured keratinocytes. Irradiation of wild-type mice with UVB caused epidermal damage such as induction of apoptosis, which was suppressed in transgenic mice expressing HSP70. UVB-induced apoptosis in cultured keratinocytes was suppressed by overexpression of HSP70. Irradiation of wild-type mice with UVB decreased the cutaneous level of IB-␣ (an inhibitor of NF-B) and increased the infiltration of leukocytes and levels of pro-inflammatory cytokines and chemokines in the epidermis. These inflammatory responses were suppressed in transgenic mice expressing HSP70. In vitro, the overexpression of HSP70 suppressed the expression of pro-inflammatory cytokines and chemokines and increased the level of IB-␣ in keratinocytes irradiated with UVB. UVB induced an increase in cutaneous levels of cyclobutane pyrimidine dimers and 8-hydroxy-2-deoxyguanosine, both of which were suppressed in transgenic mice expressing HSP70. This study provides genetic evidence that HSP70 protects the epidermis from UVB-induced radiation damage. The findings here also suggest that the protective action of HSP70 is mediated by anti-apoptotic, anti-inflammatory, and anti-DNA damage effects.The skin can be structurally classified into several layers, including the most apical layer, the epidermis, containing large numbers of keratinocytes, and a second layer, immediately under this, the dermis, which has a high fibroblast content (1). Skin provides a major interface between the environment and the body and is constantly exposed to an array of physical and chemical stressors. Therefore, in addition to intrinsic causes, harmful exogenous causes are involved in the process of skin damage. Among exogenous harmful agents, UV irradiation is the most relevant to skin damage (photo-damage). UV light can be separated, based on wavelength, into three categories: UVA (320 -400 nm), UVB (290 -320 nm), and UVC (100 -290 nm). Of these, the celldamaging effect of UVA is relatively weak, whereas most UVC is absorbed by the ozone layer (2). Thus, UVB seems to play the central role in photo-damage, such as clinical sunburn, hyperpigmentation, erythema, plaque-like thickening, loss of skin tone, deep furrowing, and fine wrinkle formation, all of which constitute both clinical and cosmetic problems. Furthermore, UVB irradiation induces the development of skin cancer (photo-carcinogenesis) (3). UVB-induced photodamage and photo-carcinogenesis both involve epidermal damage (such as induction...

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Prostaglandin E2 Protects Gastric Mucosal Cells from Apoptosis via EP2 and EP4 Receptor Activation

Cited by 135 publications

References 45 publications

Proanthocyanidins Inhibit In vitro and In vivo Growth of Human Non–Small Cell Lung Cancer Cells by Inhibiting the Prostaglandin E2 and Prostaglandin E2 Receptors

Proanthocyanidins Inhibit In vitro and In vivo Growth of Human Non–Small Cell Lung Cancer Cells by Inhibiting the Prostaglandin E2 and Prostaglandin E2 Receptors

Protection against Fas-induced liver apoptosis in transgenic mice expressing cyclooxygenase 2 in hepatocytes

Prevention of UVB Radiation-induced Epidermal Damage by Expression of Heat Shock Protein 70

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