Ironjustic
Sun, May-25-08, 06:16
Resveratrol induces apoptosis in K562 (chronic myelogenous
leukemia) cells by targeting a key survival protein, heat
shock protein 70 Authors: Chakraborty, Prabir K.1; Mustafi,
Soumyajit Banerjee1; Ganguly, Sudipto2; Chatterjee, Mitali2;
Raha, Sanghamitra
Source: Cancer Science, Volume 99, Number 6, June 2008 , pp.
1109-1116(8)
Publisher: Blackwell Publishing Abstract:
Chronic myelogenous leukemia (CML) is a myeloproliferative
disease associated with a characteristic chromosomal
translocation called the Philadelphia chromosome. This results
in the expression of the Bcr-Abl fusion protein, a
constitutively active protein tyrosine kinase. Although there
are a few treatment options with Bcr-Abl kinase inhibitors,
drug resistance is often encountered. One of the major
obstacles in overcoming drug resistance in CML is the high
endogenous levels of heat shock protein 70 (Hsp70).
Resveratrol is a phytoalexin produced by several plants. We
studied the chemotherapeutic effects and mode of action of
resveratrol on K562 (CML) cells. Resveratrol induced apoptosis
in K562 cells in a time-dependent manner. This was established
by increased annexin V binding, corroborated with an enhanced
caspase-3 activity and a rise in the sub-G0/G1 population.
Resveratrol treatment also caused suppression of Hsp70 both in
mRNA and protein levels. The downregulation of Hsp70 by
resveratrol exposure was correlated with a diminished presence
of heat shock factor 1 (HSF1) in the nucleus, and the
downregulation of transcriptional activity of HSF1. High
endogenous levels of Hsp70 have been found to be a deterrent
for sensitivity to chemotherapy. We show here that resveratrol
could considerably enhance the apoptosis induction in K562
cells by 17-allylamino-17-demethoxygeldanamycin, an anticancer
agent that inhibits Hsp90 but augments Hsp70 levels. We
conclude that resveratrol significantly downregulated Hsp70
levels through inhibition of HSF1 transcriptional activity and
appreciably augmented the pro-apoptotic effects of
17-allylamino-17- demethoxygeldanamycin. (Cancer Sci 2008; 99:
1109-1116) Document Type: Research article
DOI: 10.1111/j.1349-7006.2008.00809.x
Affiliations: 1: Crystallography and Molecular Biology
Division, Saha Institute of Nuclear Physics, 1/AF Bidhan
Nagar, Kolkata-700064; 2: Department of Pharmacology,
Institute of Post Graduate Medical Education and Research,
244B Acharya JC Bose Road, Kolkata-700020, India
-----------------
Researchers Show Resveratrol Works In The Brain By Metal
Chelating Effects
Researchers now convincingly show that, via its iron-chelating
effects, resveratrol is able to cross barriers that protect
the brain from entry of toxins (blood/brain barrier) and
reduce oxidation (spoilage) of fats and increase the activity
of protective antioxidant enzymes in the brain of healthy
rodents. The research has application for age-related brain
disorders such as Alzheimer's and Parkinson's disease.
Resveratrol decreased malondialdehyde (an end product of
oxidation of fats) in brain tissues by -300%. Doses ranging
(in human equivalents) from 87.5 to 875 milligrams were
effective in this regard. Higher doses were not more
effective.
Resveratrol also significantly increased the activity of
antioxidant enzymes superoxide dismutase, catalase and
peroxidase by 160%, 270% and 210% (see above chart). The forms
of most of these protective enzymes were iron-controlling
proteins, confirming that resveratrol's primary action is via
its ability to control metallic metals. Loose (free) iron
causes tissue damage in all forms of age-related brain
disease. While a relatively high dose of resveratrol was shown
to be most effective (875 milligrams human equivalent dose),
this was only a 7-day study. It is expected that a life-long
accumulation of iron in brain tissues will require a high
loading dose and a lower maintenance dose. The current fad of
ultra-high dose resveratrol supplementation may be beneficial
initially, but lead to anemias over longer term use.
-Resveratrol News April 2007
http://www.resveratrolnews.com/page77.htm
Who loves ya. Tom
Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
* This feature is in beta and some links may initially be
displayed as numbers instead of article titles. Clicking on
any of the links will take you to the recommended articles,
regardless of the display of the link.
leukemia) cells by targeting a key survival protein, heat
shock protein 70 Authors: Chakraborty, Prabir K.1; Mustafi,
Soumyajit Banerjee1; Ganguly, Sudipto2; Chatterjee, Mitali2;
Raha, Sanghamitra
Source: Cancer Science, Volume 99, Number 6, June 2008 , pp.
1109-1116(8)
Publisher: Blackwell Publishing Abstract:
Chronic myelogenous leukemia (CML) is a myeloproliferative
disease associated with a characteristic chromosomal
translocation called the Philadelphia chromosome. This results
in the expression of the Bcr-Abl fusion protein, a
constitutively active protein tyrosine kinase. Although there
are a few treatment options with Bcr-Abl kinase inhibitors,
drug resistance is often encountered. One of the major
obstacles in overcoming drug resistance in CML is the high
endogenous levels of heat shock protein 70 (Hsp70).
Resveratrol is a phytoalexin produced by several plants. We
studied the chemotherapeutic effects and mode of action of
resveratrol on K562 (CML) cells. Resveratrol induced apoptosis
in K562 cells in a time-dependent manner. This was established
by increased annexin V binding, corroborated with an enhanced
caspase-3 activity and a rise in the sub-G0/G1 population.
Resveratrol treatment also caused suppression of Hsp70 both in
mRNA and protein levels. The downregulation of Hsp70 by
resveratrol exposure was correlated with a diminished presence
of heat shock factor 1 (HSF1) in the nucleus, and the
downregulation of transcriptional activity of HSF1. High
endogenous levels of Hsp70 have been found to be a deterrent
for sensitivity to chemotherapy. We show here that resveratrol
could considerably enhance the apoptosis induction in K562
cells by 17-allylamino-17-demethoxygeldanamycin, an anticancer
agent that inhibits Hsp90 but augments Hsp70 levels. We
conclude that resveratrol significantly downregulated Hsp70
levels through inhibition of HSF1 transcriptional activity and
appreciably augmented the pro-apoptotic effects of
17-allylamino-17- demethoxygeldanamycin. (Cancer Sci 2008; 99:
1109-1116) Document Type: Research article
DOI: 10.1111/j.1349-7006.2008.00809.x
Affiliations: 1: Crystallography and Molecular Biology
Division, Saha Institute of Nuclear Physics, 1/AF Bidhan
Nagar, Kolkata-700064; 2: Department of Pharmacology,
Institute of Post Graduate Medical Education and Research,
244B Acharya JC Bose Road, Kolkata-700020, India
-----------------
Researchers Show Resveratrol Works In The Brain By Metal
Chelating Effects
Researchers now convincingly show that, via its iron-chelating
effects, resveratrol is able to cross barriers that protect
the brain from entry of toxins (blood/brain barrier) and
reduce oxidation (spoilage) of fats and increase the activity
of protective antioxidant enzymes in the brain of healthy
rodents. The research has application for age-related brain
disorders such as Alzheimer's and Parkinson's disease.
Resveratrol decreased malondialdehyde (an end product of
oxidation of fats) in brain tissues by -300%. Doses ranging
(in human equivalents) from 87.5 to 875 milligrams were
effective in this regard. Higher doses were not more
effective.
Resveratrol also significantly increased the activity of
antioxidant enzymes superoxide dismutase, catalase and
peroxidase by 160%, 270% and 210% (see above chart). The forms
of most of these protective enzymes were iron-controlling
proteins, confirming that resveratrol's primary action is via
its ability to control metallic metals. Loose (free) iron
causes tissue damage in all forms of age-related brain
disease. While a relatively high dose of resveratrol was shown
to be most effective (875 milligrams human equivalent dose),
this was only a 7-day study. It is expected that a life-long
accumulation of iron in brain tissues will require a high
loading dose and a lower maintenance dose. The current fad of
ultra-high dose resveratrol supplementation may be beneficial
initially, but lead to anemias over longer term use.
-Resveratrol News April 2007
http://www.resveratrolnews.com/page77.htm
Who loves ya. Tom
Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
* This feature is in beta and some links may initially be
displayed as numbers instead of article titles. Clicking on
any of the links will take you to the recommended articles,
regardless of the display of the link.