RRC ID 61528
Author 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.
Title Ellagitannins from Punica granatum leaves suppress microsomal prostaglandin E synthase-1 expression and induce lung cancer cells to undergo apoptosis.
Journal Biosci Biotechnol Biochem
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.
Volume 84(4)
Pages 757-763
Published 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
Human and Animal Cells A549(RCB0098)