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Prostate carcinoma and green tea: PSA‐triggered basement membrane degradation and MMP‐2 activation are inhibited by (−)epigallocatechin‐3‐gallate
Author(s) -
Pezzato Elga,
Sartor Luigi,
Dell'Aica Isabella,
Dittadi Ruggero,
Gion Massimo,
Belluco Claudio,
Lise Mario,
Garbisa Spiridione
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20460
Subject(s) - matrix metalloproteinase , basement membrane , gallate , epigallocatechin gallate , cancer research , degradation (telecommunications) , catechin , chemistry , carcinoma , medicine , polyphenol , biochemistry , pathology , nuclear chemistry , antioxidant , telecommunications , computer science
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. © 2004 Wiley‐Liss, Inc.