title: (-)-Epigallocatechin-3-gallate, a green tea-derived catechin, synergizes with celecoxib to inhibit IL-1-induced tumorigenic mediators by human pancreatic adenocarcinoma cells Colo357.
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.
authors.affiliation: Institute of Medical Biochemistry and Molecular Biology, University of Greifswald, D-17487 Greifswald, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Härdtner
authors.forename: Gabriele
authors.initials: G
authors.lastname: Multhoff
authors.forename: Werner
authors.initials: W
authors.lastname: Falk
authors.forename: Jürgen
authors.initials: J
authors.lastname: Radons
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D028241:Camellia sinensis / Q000737:chemistry*; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068579:Celecoxib; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D007375:Interleukin-1; D011720:Pyrazoles; D013449:Sulfonamides; D002392:Catechin; C045651:epigallocatechin gallate; D051546:Cyclooxygenase 2; D020169:Caspases; D000068579:Celecoxib