* Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells.
- Aberrant epigenetic silencing of the tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) gene that negatively regulates matrix metalloproteinases (MMPs) activity has been implicated in the pathogenesis and metastasis of breast cancer. In the present study, we demonstrate that green tea polyphenols (GTP) and its major constituent, epigallocatechin-3-gallate (EGCG) mediate epigenetic induction of TIMP-3 levels and play a key role in suppressing invasiveness and gelatinolytic activity of MMP-2 and MMP-9 in breast cancer cells. Treatment of MCF-7 and MDA-MB-231 breast cancer cells with 20 µM EGCG and 10 µg/mL GTP for 72 h significantly induces TIMP-3 mRNA and protein levels. Interestingly, investigations into the molecular mechanism revealed that TIMP-3 repression in breast cancer cells is mediated by epigenetic silencing mechanism(s) involving increased activity of the enhancer of zeste homolog 2 (EZH2) and class I histone deacetylases (HDACs), independent of promoter DNA hypermethylation. Treatment of breast cancer cells with GTP and EGCG significantly reduced EZH2 and class I HDAC protein levels. Furthermore, transcriptional activation of TIMP-3 was found to be associated with decreased EZH2 localization and H3K27 trimethylation enrichment at the TIMP-3 promoter with a concomitant increase in histone H3K9/18 acetylation. Our findings highlight TIMP-3 induction as a key epigenetic event modulated by GTPs in restoring the MMP:TIMP balance to delay breast cancer progression and invasion.
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Overview of verb reduce
The verb reduce has 20 senses (first 11 from tagged texts)
1. (102) reduce, cut down, cut back, trim, trim down, trim back, cut, bring down -- (cut down on;
make a reduction in; "reduce your daily fat intake"; "The employer wants to cut back health
benefits")
2. (9) reduce -- (make less complex; "reduce a problem to a single question")
3. (5) reduce -- (bring to humbler or weaker state or condition; "He reduced the population to
slavery")
4. (3) reduce -- (simplify the form of a mathematical equation of expression by substituting one
term for another)
5. (3) reduce -- (lower in grade or rank or force somebody into an undignified situation; "She
reduced her niece to a servant")
6. (3) reduce, come down, boil down -- (be the essential element; "The proposal boils down to a
compromise")
7. (2) shrink, reduce -- (reduce in size; reduce physically; "Hot water will shrink the sweater";
"Can you shrink this image?")
8. (1) reduce -- (lessen and make more modest; "reduce one's standard of living")
9. (1) reduce, scale down -- (make smaller; "reduce an image")
10. (1) deoxidize, deoxidise, reduce -- (to remove oxygen from a compound, or cause to react with
hydrogen or form a hydride, or to undergo an increase in the number of electrons)
11. (1) reduce, tighten -- (narrow or limit; "reduce the influx of foreigners")
12. repress, quash, keep down, subdue, subjugate, reduce -- (put down by force or intimidation; "The
government quashes any attempt of an uprising"; "China keeps down her dissidents very efficiently";
"The rich landowners subjugated the peasants working the land")
13. reduce -- (undergo meiosis; "The cells reduce")
14. reduce -- (reposition (a broken bone after surgery) back to its normal site)
15. reduce -- (destress and thus weaken a sound when pronouncing it)
16. abridge, foreshorten, abbreviate, shorten, cut, contract, reduce -- (reduce in scope while
retaining essential elements; "The manuscript must be shortened")
17. boil down, reduce, decoct, concentrate -- (be cooked until very little liquid is left; "The
sauce should reduce to one cup")
18. reduce, boil down, concentrate -- (cook until very little liquid is left; "The cook reduced the
sauce by boiling it for a long time")
19. dilute, thin, thin out, reduce, cut -- (lessen the strength or flavor of a solution or mixture;
"cut bourbon")
20. reduce, melt off, lose weight, slim, slenderize, thin, slim down -- (take off weight)
Overview of adj reduced
The adj reduced has 2 senses (first 2 from tagged texts)
1. (6) decreased, reduced -- (made less in size or amount or degree)
2. (1) reduced, rock-bottom -- (well below normal (especially in price))
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