Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells

Kang, Dong Woo; Min, Gyesik; Park, Do Yoon; Hong, Ki Whan; Min, Do Sik

doi:10.3858/emm.2010.42.8.056

Cited by 28 publications

(16 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Rebamipide, a mucosal protective agent, has been used clinically for treatment of gastritis and peptic ulcers (73). Triptolide and rebamipide suppressed the expression and activity of both PLD1 and PLD2 isozymes in various cancer cells, which was followed by inhibition of the proliferation of cancer cells (74,75). Triptolide-or rebamipide-mediated PLD1 repression was due to inhibition of NFB activity.…”

Section: Compounds Down-regulating Pld Expressionmentioning

confidence: 96%

Functional Regulation of Phospholipase D Expression in Cancer and Inflammation

Kang

Choi

Min

2014

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Phospholipase D (PLD) regulates downstream effectors by generating phosphatidic acid. Growing links of dysregulation of PLD to human disease have spurred interest in therapeutics that target its function. Aberrant PLD expression has been identified in multiple facets of complex pathological states, including cancer and inflammatory diseases. Thus, it is important to understand how the signaling network of PLD expression is regulated and contributes to progression of these diseases. Interestingly, small molecule PLD inhibitors can suppress PLD expression as well as enzymatic activity of PLD and have been shown to be effective in pathological mice models, suggesting the potential for use of PLD inhibitors as therapeutics against cancer and inflammation. Here, we summarize recent scientific developments regarding the regulation of PLD expression and its role in cancer and inflammatory processes.Phospholipase D produces phosphatidic acid (PA) 2 via hydrolysis of phospholipids such as phosphatidylcholine and cardiolipin. As a lipid second messenger, PA has been implicated in a wide range of pathophysiological processes including proliferation, oncogenesis, inflammation, phagocytosis, membrane fusion, and spermatogenesis. Phosphatidylcholine-specific PLD1 and PLD2 are the classic mammalian isoforms of PLD (1, 2). Growth factor, mitogen, and inflammatory cytokines up-regulate expression and activity of PLD; however, aberrant dysregulation of PLD occurs in various cancers and inflammation-related diseases. Accordingly, it is important to understand how expression of PLD is regulated and contributes to these diseases.An association between inflammation and cancer has been observed (3) and supported by recent epidemiological data that indicated ϳ20% of cancer deaths are linked to chronic infections and persistent inflammation (4). The PLD signaling pathway provides a possible molecular link between inflammation and cancer; however, systematic investigation of PLD as a therapeutic target has only begun within the last few years with the development of small molecule PLD inhibitors and PLD knock-out mice (5-13). This review covers recent advances in the regulation of PLD expression and its role in cancer and inflammation.

show abstract

Section: Compounds Down-regulating Pld Expressionmentioning

confidence: 96%

Functional Regulation of Phospholipase D Expression in Cancer and Inflammation

Kang

Choi

Min

2014

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…A study reported that rebamipide inhibited the transactivation of NF-kB in the AGS and MKN-1 gastric cancer cells. Such PLD1 suppression may be due to the inhibition of NF-kB activity by rebamipide (22). Chrysin, a naturally occurring flavone, which is found in honey and plant extracts, has been shown to possess anticancer properties (23).…”

Section: Discussionmentioning

confidence: 99%

The impact of caffeic acid phenethyl ester, chrysin and ethanolic extracts of propolis on PLD1 gene expression in AGS cell line

Jafari-Ghahfarokhi

Jazaeri

Amini-Sarteshnizi

et al. 2019

J Herbmed Pharmacol

View full text Add to dashboard Cite

Introduction: Up-regulation of phospholipase D (PLD) is functionally related to tumorigenesis and oncogenic signals. Chrysin, caffeic acid phenethyl ester (CAPE) and ethanolic extract of propolis (EEP) are three safe compounds which have been shown to possess antiproliferative, antioxidant, anti-inflammatory and antineoplastic properties. In this study, the effects of these three compounds on PLD1 gene expression were examined in AGS cell line. Methods: After determining the appropriate concentrations of EEP, CAPE, and chrysin, AGS cells were cultured in mediums with proper ratios of the compounds. AGS cells were maintained in exponential growth and the culture mediums refreshed every other day. Finally, after extracting total RNA from AGS cells, real-time PCR was performed to evaluate the mRNA expression of PLD1 in the presence of each compound. Results: CAPE decreased the mRNA level of PLD1 gene in a dose-dependent manner. A solution with 30 μM concentration of CAPE was the effective dose in comparison to control group as well as 15 and 20 μM concentrations of the compound, whereas no changes were observed in the presence of EEP and chrysin. Conclusion: Taken together, the results of the study indicated that CAPE might exert its anti-neoplastic effect by targeting PLD1 expression in AGS cell line.

show abstract

“…In the same study, it has been reported that PLD1 and PLD2 are targets of the Wnt/␤-catenin pathway (83)(84)(85). A potential therapeutic target for osteolytic bone metastases in lung cancer patients has been proposed (86).…”

Section: Recent Developments In Cancer and Pld Researchmentioning

confidence: 96%

Phospholipase D in Cell Signaling: From a Myriad of Cell Functions to Cancer Growth and Metastasis

Gómez‐Cambronero

2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Phospholipase D (PLD) enzymes play a double vital role in cells: they maintain the integrity of cellular membranes and they participate in cell signaling including intracellular protein trafficking, cytoskeletal dynamics, cell migration, and cell proliferation. The particular involvement of PLD in cell migration is accomplished: (a) through the actions of its enzymatic product of reaction, phosphatidic acid, and its unique shape-binding role on membrane geometry; (b) through a particular guanine nucleotide exchange factor (GEF) activity (the first of its class assigned to a phospholipase) in the case of the mammalian isoform PLD2; and (c) through protein-protein interactions with a wide network of molecules: Wiskott-Aldrich syndrome protein (WASp), Grb2, ribosomal S6 kinase (S6K), and Rac2. Further, PLD interacts with a variety of kinases (PKC, FES, EGF receptor (EGFR), and JAK3) that are activated by it, or PLD becomes the target substrate. Out of these myriads of functions, PLD is becoming recognized as a major player in cell migration, cell invasion, and cancer metastasis. This is the story of the evolution of PLD from being involved in a large number of seemingly unrelated cellular functions to its most recent role in cancer signaling, a subfield that is expected to grow exponentially.

show abstract

Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells

Cited by 28 publications

References 29 publications

Functional Regulation of Phospholipase D Expression in Cancer and Inflammation

Functional Regulation of Phospholipase D Expression in Cancer and Inflammation

The impact of caffeic acid phenethyl ester, chrysin and ethanolic extracts of propolis on PLD1 gene expression in AGS cell line

Phospholipase D in Cell Signaling: From a Myriad of Cell Functions to Cancer Growth and Metastasis

Contact Info

Product

Resources

About