Green tea constituent epigallocatechin-3-gallate selectively inhibits COX-2 without affecting COX-1 expression in human prostate carcinoma cells

Abstract

Overexpression of cyclooxygenase (COX)-2 has been implicated in many pathologic conditions, including cancer. One practical inference of this finding is that sustained inhibition of COX-2 could serve as a promising target for prevention or therapy of cancer. Conventional nonsteroidal antiinflammatory drugs (NSAIDs) and recently developed COX-2-specific inhibitors have shown considerable promise in prevention of some forms of human cancer; however, its application is limited due to severe toxic side effects on normal cells. Therefore, there is a need to define novel, nontoxic dietary constituents with proven chemopreventive effects through other pathways that also possess COX-2 but not COX-1 inhibitory activity. Recent studies on green tea and its major polyphenolic constituent (-)epigallocatechin-3-gallate (EGCG) have established its remarkable cancer preventive and some cancer therapeutic effects. Here, we show that EGCG inhibits COX-2 without affecting COX-1 expression at both the mRNA and protein levels, in androgen-sensitive LNCaP and androgen-insensitive PC-3 human prostate carcinoma cells. Based on our study, it is tempting to suggest that a combination of EGCG with chemotherapeutic drugs could be an improved strategy for prevention and treatment of prostate cancer.

Green tea polyphenol stimulates cancer preventive effects of celecoxib in human lung cancer cells by upregulation of GADD153 gene

“…33 So GADD153 is an important factor involved not only in killing cancer cells but also in the anticarcinogenic process, where it downregulates cell growth and survival. Although EGCG also has an inhibitory activity of COX-2, 34 we assume that COX-2 independent mechanisms may be involved in the synergistic induction of GADD153 gene expression and apoptosis: Cotreatment with EGCG plus celecoxib showed only additive effects on inhibition of COX-2 activity in vitro (unpublished results), and sulindac sulfone (an inactive metabolite of sulindac in COX inhibition) also showed synergistic effects similar to sulindac sulfide (an active metabolite) by cotreatment with EGCG. 7 Our assumption is supported by previous reports that celecoxib and other COX-2 inhibitors induced apoptosis independent of COX-2 activity.…”

Pancreatic cancer: Pathogenesis, prevention and treatment

“…By targeting multiple signaling pathways including MAPK, EGFR and NF-κB, EGCG is able to inhibit the malignant transformation of epidermal cell lines, to inhibit cell growth, and to induce apoptosis in a number of cancer cells including pancreatic cancer (Mukhtar and Ahmad, 1999;Khan et al, 2006;Qanungo et al, 2005). EGCG also selectively inhibits COX-2 without affecting COX-1 expression (Hussain et al, 2005) and down-regulates K-ras (Lyn-Cook et al, 1999), suggesting its effects on the inactivation of oncogenes. Furthermore, the treatment of PANC1, Mia-PaCa-2, and BxPC-3 pancreatic cell lines with EGCG caused significant suppression of the invasive ability of the pancreatic cancer cells (Takada et al, 2002).…”

Epigallocatechin-3-Gallate Has an Anti-Platelet Effect in a Cyclic AMP-Dependent Manner

“…Accordingly, inhibition of the plate-loyl group at the 3' position of catechin, which is known to have anti-platelet [13][14][15][16] , anti-oxidative 17) , anti-inflammatory 18) , anti-carcinogenic 19) , anti-hypertensive 20) , and various biological effects 21) . In addition, it is known that EGCG has anti-platelet activity by inhibiting p38 mitogen-activated protein kinase and extracellular signal-regulated kinase-1/2 13) and by reducing thrombin-induced [Ca 2＋ ]i increase via inhibition of Syk and Lyn activities 14) .…”