Prostate carcinoma and green tea: (-)epigallocatechin-3-gallate inhibits inflammation-triggered MMP-2 activation and invasion in murine TRAMP model.

Green tea infusion has been shown to inhibit metastatic spreading of the transgenic adenocarcinoma of mouse prostate (TRAMP). Investigation on the molecular mechanisms triggered by the main green tea flavonoid, (-)epigallocatechin-3-gallate (EGCG), shows that EGCG restrains TRAMP-C1 cell proliferation in a dose-dependent manner, at concentrations (IC(50) < 0.2 microM) equivalent to those measured in the plasma of moderate green-tea drinkers.

Hyperforin inhibits cancer invasion and metastasis.

Hyperforin (Hyp), the major lipophilic constituent of St. John's wort, was assayed as a stable dicyclohexylammonium salt (Hyp-DCHA) for cytotoxicity and inhibition of matrix proteinases, tumor invasion, and metastasis. Hyp-DCHA triggered apoptosis-associated cytotoxic effect in both murine (C-26, B16-LU8, and TRAMP-C1) and human (HT-1080 and SK-N-BE) tumor cells; its effect varied, with B16-LU8, HT-1080, and C-26 the most sensitive (IC50 = 5 to 8 micromol/L).

Potent inhibitors of anthrax lethal factor from green tea.

The anthrax lethal factor (LF) has a major role in the development of anthrax. LF is delivered by the protective antigen (PA) inside the cell, where it exerts its metalloprotease activity on the N-terminus of MAPK-kinases. PA+LF are cytotoxic to macrophages in culture and kill the Fischer 344 rat when injected intravenously.

Functional in vivo gene transfer into the myofibers of adult skeletal muscle.

The postmitotic nature and longevity of skeletal muscle fibers permit stable expression of any transfected gene. Direct in vivo injection of plasmid DNA, in both adult and regenerating muscles, is a safe, inexpensive, and easy approach. Here we present an optimized electroporation protocol based on the use of spatula electrodes to transfer cDNA in vivo into the adult myofibers of an anatomically defined muscle, which could be functionally characterized.

Proteinase-3 directly activates MMP-2 and degrades gelatin and Matrigel; differential inhibition by (-)epigallocatechin-3-gallate.

Proteinase-3 (PR-3), a serine-proteinase mainly expressed by polymorphonuclear leukocytes (PMNs), can degrade a variety of extracellular matrix proteins and may contribute to a number of inflammation-triggered diseases. Here, we show that in addition to Matrigel(TM) components, PR-3 is also able to degrade denatured collagen and directly activate secreted but not membrane-bound pro-MMP-2, a matrix metallo-proteinase instrumental to cellular invasion. In contrast, following addition of purified PR-3 or PMNs to HT1080 tumor cells, dose-dependent inhibition of in vitro Matrigel(TM) invasion is registered.

Green tea epigallocatechin-3-gallate inhibits platelet signalling pathways triggered by both proteolytic and non-proteolytic agonists.

Epigallocatechin-3-gallate (EGCG), a component of green tea, inhibits human platelet aggregation and cytosolic [Ca(2+)](c) increases more strongly when these processes are induced by thrombin than by the non-proteolytic thrombin receptor activating peptide (TRAP), thromboxane mimetic U46619, or fluoroaluminate. In line with the previously demonstrated EGCG anti-proteolytic activity, a marked inhibition on aggregation is obtained by pre-incubation of thrombin with EGCG prior to addition to cellular suspension. The catechin also reduces cellular Ca(2+) influx following thapsigargin-induced calcium emptying of endoplasmic reticulum, and the agonist-promoted cellular protein tyrosine phosphorylation.

Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis.

Neutrophils play an essential role in host defense and inflammation, but the latter may trigger and sustain the pathogenesis of a range of acute and chronic diseases. Green tea has been claimed to exert anti-inflammatory properties through unknown molecular mechanisms. We have previously shown that the most abundant catechin of green tea, (-)epigallocatechin-3-gallate (EGCG), strongly inhibits neutrophil elastase.

(-)Epigallocatechin-3-gallate directly inhibits MT1-MMP activity, leading to accumulation of nonactivated MMP-2 at the cell surface.

Consumption of green tea has been associated with prevention of cancer development, metastasis, and angiogenesis. Given the crucial role of the matrix metallo-proteinase-2 (MMP-2) on the degradation of the extracellular matrix instrumental to invasion, we examined the effect of the main flavanol present, (-)epigallocatechin-3-gallate (EGCG), on membrane-type 1 MMP (MT1-MMP), the receptor/activator of MMP-2. In-solution fluorimetric assay with activated MT1-MMP and gelatin-zymography with MT1-MMP catalytic domain alone and pro-MMP-2 activation by the same domain revealed dose-dependent inhibition of MT1-MMP at EGCG concentrations slightly lower than that reported to inhibit MMP-2 and MMP-9.

L-Carnitine: a potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure.

Skeletal muscle in congestive heart failure is responsible for increased fatigability and decreased exercise capacity. A specific myopathy with increased expression of fast-type myosins, myocyte atrophy, secondary to myocyte apoptosis triggered by high levels of circulating tumor necrosis factor-alpha (TNF-alpha) has been described. In an animal model of heart failure, the monocrotaline-treated rat, we have observed an increase of apoptotic skeletal muscle nuclei.