Prostate carcinoma and green tea: PSA‐triggered basement membrane degradation and MMP‐2 activation are inhibited by (−)epigallocatechin‐3‐gallate

Abstract

Prostate-specific antigen (PSA) is a serine-protease that, in addition to cleaving semenogelins in the seminal coagulum, is able to cleave extracellular matrix glycoproteins, thereby affecting cell migration and metastasis. We here report some new activities of PSA that deserve careful consideration in the cancer context: degradation of gelatin, degradation of type IV collagen in reconstituted basement membrane (Matrigel) and activation of progelatinase A (MMP-2), but not pro-MMP-9, in a cell-free system. Since consumption of green tea has been reported to lower the risk of prostate cancer, we investigated the effects of the major flavanol of green tea, (؊)epigallocatechin-3-gallate (EGCG), on expression and activity of PSA by prostate carcinoma cells. In addition to restraint of PSA expression, EGCG was found to inhibit in a dose-dependent manner all the above PSA activities, at concentrations lower than the cytotoxic serine-protease inhibitor PMSF and close to levels measured in the serum following ingestion of green tea. The activity of PSA was suppressed also by the elastase released by the inflammatory leukocytes. These results highlight new PSA activities, suggest gelatin zymography as a new convenient assay for PSA, propose EGCG as natural inhibitor of prostate carcinoma aggressiveness, but also stimulate further investigation on the role of prostatic inflammation.

Does regular consumption of green tea influence expression of vascular endothelial growth factor and its receptor in aged rat erectile tissue? Possible implications for vasculogenic erectile dysfunction progression

“…This hypothesis is supported by the finding that EGCG inhibited metallo-proteinase-2 and reduced basement lamina degradation in prostate carcinoma cells (Pezzato et al 2004). In addition, EGCG has been demonstrated to possess potent antimatrix metalloproteinase activity in cancer cell cultures, also blunting the angiogenesis crucial for the growth of solid tumours (Garbisa et al 1999;Maeda et al 2003).…”

Green tea polyphenol epigallocatechin-3-gallate inhibits the endothelin axis and downstream signaling pathways in ovarian carcinoma

“…Moreover, ET-1 contributes to the acquisition of migratory and invasive phenotype by inducing the disruption of host-tumor interactions (36) and by up-regulating protease (6) and VEGF expression (8,9,13,14). Green tea polyphenols are becoming increasingly recognized for their antiangiogenic, antimetastatic (17,18), and anti-invasive properties as potent inhibitors of VEGF production (32) and MMPs, such as MMP-2 and MMP-9, in different cell types (25,37). Studies have shown that polyphenols from green tea possess antitumor and antimetastatic activity in animal xenograft and allograft model, suggesting a possible therapeutic potential (17,18).…”

Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities

“…In androgen-dependent (androgen receptor positive) LNCaP cells, EGCG contributed to anti-invasive and anti-migratory effects via the downregulation of androgen-induced uPA, MMP-2/MMP-3/MMP-9, VEGF, and Ang1/2 and upregulation of TIMP-1 [96,97]. Furthermore, EGCG inhibited the PSA-triggered basement membrane degradation and MMP-2 in Du145 and LNCaP cells [98] as well as inflammation-triggered MMP-2; invasion of mouse prostate (TRAMP)-C1 cells in transgenic adenocarcinoma has also been demonstrated [99]. These results indicated that EGCG could synergistically inhibit biomarkers associated with angiogenesis and metastasis of prostate carcinoma.…”