RRC ID |
61528
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著者 |
Toda K, Ueyama M, Tanaka S, Tsukayama I, Mega T, Konoike Y, Tamenobu A, Bastian F, Akai I, Ito H, Kawakami Y, Takahashi Y, Suzuki-Yamamoto T.
|
タイトル |
Ellagitannins from Punica granatum leaves suppress microsomal prostaglandin E synthase-1 expression and induce lung cancer cells to undergo apoptosis.
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ジャーナル |
Biosci Biotechnol Biochem
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Abstract |
Prostaglandin E2 (PGE2), which is a potent pro-inflammatory lipid mediator, is biosynthesized from arachidonic acid by cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Non-steroidal anti-inflammatory drugs (NSAIDs) are used clinically as COX inhibitors, but they have gastrointestinal and cardiovascular side-effects. Thus, the terminal enzyme mPGES-1 holds promise as the next therapeutic target. In this study, we found that the ellagitannins granatin A and granatin B isolated from pomegranate leaves, and geraniin, which is their structural analog, selectively suppressed mPGES-1 expression without affecting COX-2 in non-small cell lung carcinoma A549 cells. The ellagitannins also down-regulated tumor necrosis factor α, inducible nitric oxide synthase, and anti-apoptotic factor B-cell chronic lymphocytic leukemia/lymphoma 2, and induced A549 cells to undergo apoptosis. These findings indicate that the ellagitannins have anti-inflammatory and anti-carcinogenic effects, due to their specific suppression of mPGES-1.Abbreviations: Bcl-2: B-cell chronic lymphocytic leukemia/lymphoma 2; COX: cyclooxygenase; CRE: cAMP response element; DHHDP: dehydrohexahydroxydiphenoyl; Et2O: diethyl ether; EtOAc: ethyl acetate; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; iNOS: inducible nitric oxide synthase; mPGES-1: microsomal prostaglandin E synthase-1; n-BuOH: water-saturated n-butanol; NSAIDs: non-steroidal anti-inflammatory drugs; NF-κB: nuclear factor-κB; PG: prostaglandin; TNF: tumor necrosis factor; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling.
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巻・号 |
84(4)
|
ページ |
757-763
|
公開日 |
2020-4-1
|
DOI |
10.1080/09168451.2019.1706442
|
PMID |
31868102
|
MeSH |
A549 Cells
Apoptosis / drug effects*
Cyclooxygenase 2 / genetics
Cyclooxygenase 2 / metabolism
Humans
Hydrolyzable Tannins / pharmacology*
Lung Neoplasms / pathology*
Plant Leaves / chemistry*
Pomegranate / chemistry*
Prostaglandin-E Synthases / antagonists & inhibitors*
Prostaglandin-E Synthases / genetics
Prostaglandin-E Synthases / metabolism
RNA, Messenger / genetics
|
IF |
1.516
|
リソース情報 |
ヒト・動物細胞 |
A549(RCB0098) |