X-Message-Number: 30602
Date: Sun, 9 Mar 2008 09:37:41 -0800 (PST)
From: 
Subject: possible synergism between polyphenols, dithiotreitol,& DMSO

**SPECULATION**

[Green tea polyphenols and DMSO offered synergism in protecting
osteoblastic cells from freeze/thaw damage. Moreover green tea polyphenol
cytotoxicity has been apparently abrogated by dithiothreitol. This yields
the possibility of a further synergism between these three items.]

Chem Res Toxicol. 2008 Feb 23 [Epub ahead of print]
(-)-Epigallocatechin Gallate, A Major Constituent of Green Tea, Poisons
Human Type II Topoisomerases.
  Bandele OJ, Osheroff N.
  (-)-Epigallocatechin gallate (EGCG) is the most abundant and
biologically active polyphenol in green tea, and many of the therapeutic
benefits of the beverage have been attributed to this compound. High
concentrations of EGCG are cytotoxic and trigger genotoxic events in
mammalian cells. Although this catechin affects a number of cellular
systems, the genotoxic effects of several bioflavonoid-based dietary
polyphenols are believed to be mediated, at least in part, by their
actions on topoisomerase II. Therefore, the effects of green tea extract
and EGCG on DNA cleavage mediated by human topoisomerase IIalpha and beta
were characterized. The extract and EGCG increased levels of DNA strand
breaks generated by both enzyme isoforms. However, EGCG acted by a
mechanism that was distinctly different from those of genistein, a
dietary polyphenol, and etoposide, a widely prescribed anticancer drug. In
contrast to these agents, EGCG exhibited all of the characteristics of a
redox-dependent topoisomerase II poison that acts by covalently adducting
to the enzyme. First, EGCG stimulated DNA scission mediated by both
isoforms primarily at sites that were cleaved in the absence of
compounds. Second, exposure of EGCG to the reducing agent dithiothreitol
(DTT) prior to its addition to DNA cleavage assays abrogated the effects
of the catechin on DNA scission. Third, once EGCG stimulated
topoisomerase II-mediated DNA cleavage, exposure to DTT did not effect
levels of DNA strand breaks. Finally, EGCG inhibited the DNA cleavage
activities of topoisomerase IIalpha and beta when incubated with either
enzyme prior to the addition of DNA. Taken together, these results
provide strong evidence that EGCG is a redox-dependent topoisomerase II
poison and utilizes a mechanism similar to that of 1,4-benzoquinone.
PMID: 18293940

Biotechnol Lett. 2005 May;27(9):655-60.
Protection of osteoblastic cells from freeze/thaw cycle-induced oxidative
stress by green tea polyphenol.
  Han DW, Kim HH, Lee MH, Baek HS, Lee KY, Hyon SH, Park JC. Department
of Medical Engineering, Yonsei University College of Medicine, 134
Shinchon-dong, Seodaemun-gu, Seoul, 120-752, Korea.
  Green tea polyphenol (GTP) together with dimethylsulphoxide (DMSO) were
added to a freezing solution of osteoblastic cells (rat calvarial
osteoblasts and human osteosarcoma cells) exposed to repeated freeze/thaw
cycles (FTC) to induce oxidative stress. When cells were subjected to 3
FTCs, freezing medium containing 10% (v/v) DMSO and 500 mug GTP
ml(-1) significantly (p<0.05) suppressed cell detachment and growth
inhibition by over 63% and protected cell morphology. Furthermore, the
alkaline phosphatase activity of osteoblastic cells was appreciably
maintained after 2 and 3 FTCs in this mixture. Polyphenols may thus be of
use as a cell cryopreservant and be advantageous in such fields as cell
transplantation and tissue engineering.
PMID: 15977073

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