Prostate carcinoma and green tea: PSA-triggered basement membrane degradation and MMP-2 activation are inhibited by (-)epigallocatechin-3-gallate.
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.
Pezzato
Elga
E
Department of Experimental Biomedical Sciences, Medical School, Padova, Italy.
Sartor
Luigi
L
Dell'Aica
Isabella
I
Dittadi
Ruggero
R
Gion
Massimo
M
Belluco
Claudio
C
Lise
Mario
M
Garbisa
Spiridione
S
D000975:Antioxidants / Q000494:pharmacology*; D001485:Basement Membrane / Q000378:metabolism; D002277:Carcinoma / Q000473:pathology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000032:analysis* / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D012307:Risk Factors; D013662:Tea; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D017430:Prostate-Specific Antigen; D020778:Matrix Metalloproteinase 2