Haerdtner, Carmen and Multhoff, Gabriele and Falk, Werner and Radons, Juergen (2012) (-)-Epigallocatechin-3-gallate, a green tea-derived catechin, synergizes with celecoxib to inhibit IL-1-induced tumorigenic mediators by human pancreatic adenocarcinoma cells Colo357. EUROPEAN JOURNAL OF PHARMACOLOGY, 684 (1-3). pp. 36-43. ISSN 0014-2999, 1879-0712
Full text not available from this repository. (Request a copy)Abstract
Despite their toxic side effects prostaglandin H-2 synthase-2 (PGHS-2) inhibitors hold promise for cancer chemoprevention. In order to overcome adverse effects lower doses of PGHS-2 inhibitors could be applied in combination with other agents exhibiting complementary effects. Herein, the effects of the PGHS-2-specific inhibitor celecoxib either alone or in combination with the green tea-derived catechin (-)-epigallocatechin-3-gallate (EGCG) were studied on the expression of interleukin (IL)-1-induced tumorigenic factors in Colo357 human pancreatic adenocarcinoma cells. This approach mimics tumor-associated pancreatic inflammation which is considered as a key player in pancreatic malignancy. We found that co-incubation of Colo357 with celecoxib and EGCG synergistically diminished metabolic activity via apoptosis induction and down-regulated release of pro-angiogenic vascular endothelial growth factor (VEGF) and invasiveness-promoting matrix metalloproteinase (MMP)-2 to a maximum of 30%. Celecoxib and EGCG synergistically reduced IL-1-induced production of pro-inflammatory IL-6 and pro-angiogenic IL-8 to 23-50%. Celecoxib dose-dependently increased PGHS-2 levels. Whereas EGCG was able to compensate for celecoxib-mediated increase of PGHS-2, it failed to potentiate celecoxib-mediated suppression of prostaglandin E-2 (PGE(2)) release. Thus, in Colo357, EGCG synergistically boosts celecoxib-mediated effects and reduces the levels of celecoxib required to elicit beneficial effects on tumorigenic mediators by a factor of ten. (C) 2012 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN-E SYNTHASE; PROSTATE-CANCER CELLS; IN-VITRO; CARDIOVASCULAR RISK; SIGNALING PATHWAYS; CARCINOMA CELLS; POLYPHENON-E; TUMOR-CELLS; NK CELLS; Pancreatic carcinoma; Celecoxib; EGCG; IL-1; Colo357; PGHS-2 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 May 2020 06:42 |
| Last Modified: | 12 May 2020 06:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18598 |
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