ELIZA

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475194 occurrences (No.33 in the rank) during 5 years in the PubMed. [cache]

95) Silymarin reduced PGE2 -induced CREB phosphorylation and CRE-promoter activity.

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PMID:24127286 DOI:10.1002/mc.22092

2015 Molecular carcinogenesis

* Silymarin suppresses the PGE2 -induced cell migration through inhibition of EP2 activation; G protein-dependent PKA-CREB and G protein-independent Src-STAT3 signal pathways.

- Silymarin has been known as a chemopreventive agent, and possesses multiple anti-cancer activities including induction of apoptosis, inhibition of proliferation and growth, and blockade of migration and invasion. However, whether silymarin could inhibit prostaglandin (PG) E2 -induced renal cell carcinoma (RCC) migration and what are the underlying mechanisms are not well elucidated. Here, we found that silymarin markedly inhibited PGE2 -stimulated migration. PGE2 induced G protein-dependent CREB phosphorylation via protein kinase A (PKA) signaling, and PKA inhibitor (H89) inhibited PGE2 -mediated migration. Silymarin reduced PGE2 -induced CREB phosphorylation and CRE-promoter activity. PGE2 also activated G protien-independent signaling pathways (Src and STAT3) and silymarin reduced PGE2 -induced phosphorylation of Src and STAT3. Inhibitor of Src (Saracatinib) markedly reduced PGE2 -mediated migration. We found that EP2, a PGE2 receptor, is involved in PGE2 -mediated cell migration. Down regulation of EP2 by EP2 siRNA and EP2 antagonist (AH6809) reduced PGE2 -inudced migration. In contrast, EP2 agonist (Butaprost) increased cell migration and silymarin effectively reduced butaprost-mediated cell migration. Moreover, PGE2 increased EP2 expression through activation of positive feedback mechanism, and PGE2 -induced EP2 expression, as well as basal EP2 levels, were reduced in silymarin-treated cells. Taken together, our study demonstrates that silymarin inhibited PGE2 -induced cell migration through inhibition of EP2 signaling pathways (G protein dependent PKA-CREB and G protein-independent Src-STAT3).

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(1)70 of	(13)6 patterns	(25)3 but	(37)2 functional
(2)54 null	(14)5 may	(26)3 changes	(38)2 increased
(3)49 and	(15)5 using	(27)3 for	(39)2 induces
(4)45 in	(16)5 with	(28)3 measured	(40)2 level
(5)17 was	(17)4 at	(29)3 through	(41)2 or
(6)11 against	(18)4 levels	(30)2 Questionnaire	(42)2 over
(7)10 during	(19)4 on	(31)2 after	(43)2 promotion
(8)9 (PA)	(20)4 which	(32)2 between	(44)2 resumption
(9)8 is	(21)4 while	(33)2 calcium	(45)2 than
(10)7 to	(22)3 among	(34)2 compared	(46)2 that
(11)7 were	(23)3 are	(35)2 decreased	(47)2 via
(12)6 by	(24)3 as	(36)2 diary	(48)2 when

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--- WordNet output for activity --- =>活動, 活躍, 働き, 動き, 活気 Overview of noun activity The noun activity has 6 senses (first 3 from tagged texts) 1. (43) activity -- (any specific behavior; "they avoided all recreational activity") 2. (36) action, activity, activeness -- (the state of being active; "his sphere of activity"; "he is out of action") 3. (13) bodily process, body process, bodily function, activity -- (an organic process that takes place in the body; "respiratory activity") 4. activity -- ((chemistry) the capacity of a substance to take part in a chemical reaction; "catalytic activity") 5. natural process, natural action, action, activity -- (a process existing in or produced by nature (rather than by the intent of human beings); "the action of natural forces"; "volcanic activity") 6. activeness, activity -- (the trait of being active; moving or acting rapidly and energetically; "the level of activity declines with age") --- WordNet end ---