190,000 compounds were used to selectinhibitors by Biosym LUDI and DOCKINGprograms. In these calculations, the relative
position of inhibitor and receptor (uPA)with the minimum potential energy repre-
Epidemiological studies suggest that the the cathechins, destroying any beneficial sents the most probable way of binding.
effects1. Several mechanisms of anticancer
activity of cathechins have been postulated,
but none seems universal for all cancers1–3.
reduced by green, but not black, tea1. Here
binds to uPA, blocking His 57 and Ser 195
subsequently demonstrated that one of the
loop of uPA (Fig. 1a). Such localization of
tumour size or even cause complete remis-
sion of cancers in mice4,5. The known uPA
uPA to recognize its substrates and inhibit
inhibitors are unlikely to be used in anti-
activity in the presence of different concen-
inhibitors by computer modelling using the
active site of uPA as a template. Coordinates
cathechin (EGC) and epicathechin-3 gallate
of human uPA were kindly provided by trozyme, which releases a chromogen on
C. Phillips6; National Cancer Institute, specific cleavage by uPA. EGCG from two
different suppliers showed almost identical
to inhibit uPA with that of a well-knowninhibitor, amiloride, and a control samplewhere no inhibitors were used (Fig. 1b).
EGCG is a weaker inhibitor than amiloride,but can be consumed in much higher doseswithout any toxicological effects. Amilorideis administered in a maximum dose of 20 mg per day, whereas a single cup of teacontains 150 mg EGCG, and some tealovers consume up to 10 cups a day1.
likely to have a physiological effect andcould reduce incidence of cancer in humansor the size of cancers already formed.
Theoretically, EGCG might inhibit cancerformation in many different ways; however,we postulate that the well-known anti-cancer activity of green tea is driven by inhi-
bition of uPA, one of the most frequently
overexpressed enzymes in human cancers.
Steven H. Selman
Department of Urology, and *Department of
Physiology and Molecular Medicine,
1. Yang, C. S. et al. J. Natl Cancer Inst. 85,
UK (purple diamonds); amiloride (green squares), and control sample (orange circles). Experimental mixtures
2. Stoner, G. D. & Mukhtar, H. J. Cell. Biochem. 22,
(50 mM Tris with 0.01% Tween 80, 0.01% PEG 8000 buffer; pH 8.8) were incubated with 1 Ȗg of uPA and
3. Fujiki, H. et al. Prev. Med. 21,
4. Harvey, S. R. et al. Clin. Exp. Metastasis 6,
decreasing amounts of inhibitor for 15 min. 100 Ȗl of this mixture was incubated in a 96-well microplate with
5. Jankun, J., Keck, R. W., Skrzypczak-Jankun, E. & Swiercz, R.
50 Ȗl (2.5 mM) Spectrozyme (carbobenzyl-L-(ȍ)-Glu(Ȋ-t-BuO)-Gly-Arg-p-nitroanilide.2C H OH from American
Cancer Res. 57,
Diagnostica Inc., Greenwich, Connecticut), for 10 min. Absorbance, which is inversely proportional to the uPA
6. Spargon, G. et al. Structure 3,
inhibitory activity7, was measured at 405 nm on a microplate reader.
7. Achbarou, A. et al. Cancer Res. 54,
Nature Macmillan Publishers Ltd 1997
DEMANDA DE FRAUDE ELECTORAL Línea telefónica directa de Fraude al Votante 1-877-868-3737 Conforme a la sección 97.012(15), Estatutos de la Florida, la División Electoral tiene autoridad para llevar a cabo investigaciones preliminares sobre cualquier alegato de irregularidades o fraude que involucren registro de votantes o votación, o petición de candidato o emisión de actividades de
Features • Truly compact: 4.60” diameter – same as a CD! • UV ranges simultaneously– UVA, UVB, UVC, UVV Applications • Measure UV curing system performance • Establish UV level for proper curing radiometer, the operator can immediately quantify the process. After product is cured satisfactorily, the operator exposes the radiometer to the same UV process. The UV le