Team:Rice University/BACKGROUND

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Revision as of 22:14, 29 October 2008

OUR TEAM ::: SUMMARY ::: INTRODUCTION ::: STRATEGY ::: RESULTS ::: ONGOING WORK ::: GALLERY

In 1940, Resveratrol was identified as the active component in Cassia quniquangulata (cinnamon) extract and was shown to be responsible for the anti-inflammatory properties of Polygonum cuspidatum roots, used in traditional Chinese and Japanese medicine [1]. Since then, studies have shown that resveratrol is a member of a class of compounds called phytoalexins, which are used as a defense mechanism in plants in response to pathogens (for review, see [2]). Grapes and several types of berries (blueberries, bilberries, and cranberries) produce appreciable levels of resveratraol, and thus the main sources of resveratrol in the human diet are wine and juices [3]. The discovery of Resveratrol in wine [4], implicated a role for this compound in underlying the “French Paradox”, i.e., the observation that French exhibit a relatively low risk of cardiovascular disease even though they exhibit a diet that is high in saturated fats.

Health Benefits of Resveratrol

History of Resveratrol Citatitions on PubMed Notice Semilog Plot

A PubMed search for “resveratrol”, indicates that scientific interest in the health benefits of this phytoalexin is growing exponentially. To date, a diverse array of health benefits have been associated with resveratrol, including:

1. Improved insulin sensitivity. Resveratrol has been shown as a potent therapeutic for type 2 diabetes [5]. Pharmaceuticals based on resveratrol-like compounds for the treatment of diabetes are currently in Phase I clinical trials [6].

2. Inhibits carcinogenesis. Resveratrol induces cell death specifically in cancerous cells. This property has been demonstrated for a variety of cancers, including colon [7-9], pancreatic [10], prostate [11,12], breast [13,14], and skin [15,16] cancer. Several ongoing phase I human clinical trials are investigating resveratrol as a cancer therapy [17,18]

3. Extended lifespan. Resveratrol mimics the effects of caloric restriction in mammals and has been shown to extend lifespans in invertebrates [19,20], and a fish model [21]. In addition, resveratrol reduces the genetic changes associated with aging in a mammalian mouse model [22-24]. PGC-1alpha levels was decreased threefold by induction of genes for oxidative phosphorylation and mitochondrial biogenesis in wt SIRT1 mice but no change in SIRT1(-/-) MEFs [25].

4. Improved cardiovascular function. Resveratrol exhibits cardioprotective effects, such as the suppression of atherosclerosis, inhibition of platelet aggregation, vasorelaxation promotion, and modulation of triglyceride blood levels [22,26-28].

5. Reduced Neurodegeneration. Mouse models of Alzheimer's and Parkinson's disease have provided evidence that resveratrol functions as a protective agent against degenerative neural diseases [29,30]. In addition, Experiments with rats, mice, and gerbils show that resveratrol administration protects against brain damage following isochemic stroke [31-33].

6. Decreases inflammation. NEED A SENTENCE OR TWO SUMMARIZING THESE CITATIONS [34,35].

Unfortunately, our understanding of resveratrol effects on cellular function is currently too limited to explain the biochemical origin of the diverse pharmacological effects that have been observed to date.

Rationale for Creating Resveratrol-Enriched Beer

One of the best sources of resveratrol is wine, with red wine having concentrations ranging from 0.1 to 14.3mg/L and white wine having concentrations ranging from <0.1 to 2.1mg/L [3]. Unfortunately, the abundance of resveratrol in this beverage is thought to be too low to allow for all of the health benefits that have been demonstrated in model organisms, beneficial effects have been shown at levels readily achieved in humans [4].

Beer is also expected to contain resveratrol. Hops that is used to flavor beer contains 0.5 to 1 µg resveratrol/g [3], and beer is produced under fermentative conditions, which is likely to prevent the air oxidation and inactivation of resveratrol from the hops. While the levels of resveratrol in beer are less than that of wine, beer represents >85% of all alcoholic beverages consumed in the US [35], and thus a better vehicle for widespread delivery of air-sensitive prophylactics like resveratrol. To increase the level of resveratrol present in beer, we are working to engineer a brewers yeast that synthesizes resveratrol from tyrosine.

References

1: Takaoka, M. J. Of the phenolic substances of white hellebore (Veratrum grandiflorum Loes. Fil.) J. Faculty Sci. Hokkaido Imperial University. 1940; 3: 1-16.

2. Hammerschmidt, R. PHYTOALEXINS:What Have We Learned After 60 years. Annu. Rev. Phytopathol. 1999; 37:285–306

3. Baur, J. A. and Sinclair, D. A. Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews Drug Discovery. 2006; 5: 493-506.

4. Renaud, S. and Gueguen, R. The French Paradox and wine drinking. Novartis Found. Sympos. 1998; 216:208-217.

5. Milne JC, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov 29;450(7170):712-6.

6. http://www.sirtrispharma.com/pipeline-SRT501.html

7. Juan ME, et al. Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT-29 human colorectal carcinoma cells. J Agric Food Chem. 2008 Jun 25;56(12):4813-8. Epub 2008 Jun 4.

8. Saiko P, et al. Novel resveratrol analogs induce apoptosis and cause cell cycle arrest in HT29 human colon cancer cells: inhibition of ribonucleotide reductase activity. Oncol Rep. 2008 Jun;19(6):1621-6.

9. Marel AK, et al. Inhibitory effects of trans-resveratrol analogs molecules on the proliferation and the cell cycle progression of human colon tumoral cells. Mol Nutr Food Res. 2008 May;52(5):538-48.

10. Bernhaus A, et al. Antitumor effects of KITC, a new resveratrol derivative, in AsPC-1 and BxPC-3 human pancreatic carcinoma cells. Invest New Drugs. 2008 Oct 8. [Epub ahead of print]

11. Seeni A, et al. Suppression of Prostate Cancer Growth by Resveratrol in The Transgenic Rat for Adenocarcinoma of Prostate (TRAP) Model. Asian Pac J Cancer Prev. 2008 Jan-Mar;9(1):7-14.

12. Horvath Z, et al. Novel resveratrol derivatives induce apoptosis and cause cell cycle arrest in prostate cancer cell lines. Anticancer Res. 2007 Sep-Oct;27(5A):3459-64.

13. Filomeni G, et al. trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways. Genes Nutr. 2007 Dec;2(3):295-305. Epub 2007 Oct 18.

14. Schlachterman A, et al. Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model. Transl Oncol. 2008 Mar;1(1):19-27.

15. Jang M, Cai L, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997 Jan 10;275(5297):218-20.

16. van Ginkel PR, et al. Resveratrol inhibits uveal melanoma tumor growth via early mitochondrial dysfunction. Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1299-306.

17. http://www.clinicaltrials.gov/ct/show/NCT00256334

18. http://www.cancer.gov/clinicaltrials/CCUM-2004-0535

19. Howitz KT, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003 Sep 11;425(6954):191-6. Epub 2003 Aug 24.

20. Wood JG, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004 Aug 5;430(7000):686-9.

21. Valenzano DR, et al. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol. 2006 Feb 7;16(3):296-300.

22. Barger JL, et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE. 2008 Jun 4;3(6):e2264.

23. Kode A, et al. (2007). "Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells". Am J Physiol Lung Cell Mol Physiol.

24. Baur JA, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42. Epub 2006 Nov 1.

25. M . Lagouge , C . Argmann , Z . Gerhart-Hines , H . Meziane , C . Lerin , F . Daussin , N . Messadeq , J . Milne , P . Lambert , P . Elliott. Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α . Cell , Volume 127 , Issue 6 , Pages 1109 - 1122

26. Samuel SM, et al. Akt/FOXO3a/SIRT1-mediated cardioprotection by n-tyrosol against ischemic stress in rat in vivo model of myocardial infarction: switching gears toward survival and longevity. J Agric Food Chem. 2008 Oct 22;56(20):9692-8.

27. Hwang JT, et al. Resveratrol protects ROS-induced cell death by activating AMPK in H9c2 cardiac muscle cells. Genes Nutr. 2008 Feb;2(4):323-6.

28. Gresele P, et al. Resveratrol, at concentrations attainable with moderate wine consumption, stimulates human platelet nitric oxide production. J Nutr. 2008 Sep;138(9):1602-8.

29. Kim D, et al. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J. 2007 Jul 11;26(13):3169-79. Epub 2007 Jun 21.

30. Jin F, et al. Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson's disease in rats. Eur J Pharmacol. 2008 Oct 10. [Epub ahead of print]

31. Sinha K, et al. Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats. Life Sci. 2002 Jun 28;71(6):655-65.

32. Inoue H, et al. Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice. Neurosci Lett. 2003 Dec 11;352(3):203-6.

33. Wang Q, et al. Resveratrol protects against global cerebral ischemic injury in gerbils. Brain Res. 2002 Dec 27;958(2):439-47.

34. Zhu J, et al. Anti-inflammatory effect of resveratrol on TNF-alpha-induced MCP-1 expression in adipocytes. Biochem Biophys Res Commun. 2008 May 2;369(2):471-7. Epub 2008 Feb 20.

35. Kennedy A, et al. Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol. J Lipid Res. 2008 Sep 5. [Epub ahead of print]

36. NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM LINK

1: Samuel SM, et al. Akt/FOXO3a/SIRT1-mediated cardioprotection by n-tyrosol against ischemic stress in rat in vivo model of myocardial infarction: switching gears toward survival and longevity. J Agric Food Chem. 2008 Oct 22;56(20):9692-8. Epub 2008 Oct 1. PMID: 18826227 [PubMed - in process].

SUMMARY ::: BACKGROUND ::: STRATEGY ::: CONSTRUCTS ::: RESULTS ::: ONGOING WORK ::: OUR TEAM ::: NOTEBOOK ::: GALLERY

@@ Line 21: / Line 21: @@
 === '''History of Resveratrol''' ===
 [[Image:trans-resveratrol.jpg|right|frame|none|trans-Resveratrol]]
-In 1940, Resveratrol was identified as the active component in ''Cassia quniquangulata'' (cinnamon) extract and was shown to be responsible for the anti-inflammatory properties of Polygonum cuspidatum roots, used in traditional Chinese and Japanese medicine [1]. Since then, studies have shown that resveratrol is a member of a class of compounds called phytoalexins, which are used as a defense mechanism in plants in response to pathogens (for review, see [2]). Grapes and several types of berries (blueberries, bilberries, and cranberries) produce appreciable levels of resveratraol, and thus the main sources of resveratrol in the human diet are wine and juices [3]. The discovery of Resveratrol in wine [4-5], implicated a role for this compound in underlying the “French Paradox”, i.e., the observation that French exhibit a relatively low risk of cardiovascular disease even though they exhibit a diet that is high in saturated fats.
+In 1940, Resveratrol was identified as the active component in ''Cassia quniquangulata'' (cinnamon) extract and was shown to be responsible for the anti-inflammatory properties of Polygonum cuspidatum roots, used in traditional Chinese and Japanese medicine [1]. Since then, studies have shown that resveratrol is a member of a class of compounds called phytoalexins, which are used as a defense mechanism in plants in response to pathogens (for review, see [2]). Grapes and several types of berries (blueberries, bilberries, and cranberries) produce appreciable levels of resveratraol, and thus the main sources of resveratrol in the human diet are wine and juices [3]. The discovery of Resveratrol in wine [4], implicated a role for this compound in underlying the “French Paradox”, i.e., the observation that French exhibit a relatively low risk of cardiovascular disease even though they exhibit a diet that is high in saturated fats.
@@ Line 28: / Line 28: @@
 ==='''Health Benefits of Resveratrol''' ===
 [[Image:RSV.jpg|left|thumb|250x|History of Resveratrol Citatitions on PubMed  Notice Semilog Plot]]
-A PubMed search for “resveratrol”, indicates that scientific interest in the health benefits of resveratrol is growing exponentially. To date, a diverse array of health benefits have been associated with resveratrol, including:
+A PubMed search for “resveratrol”, indicates that scientific interest in the health benefits of this phytoalexin is growing exponentially. To date, a diverse array of health benefits have been associated with resveratrol, including:
 <BR>
-<B>1. Improved insulin sensitivity.</B> Resveratrol has been shown as a potent therapeutic for type 2 diabetes [27]. Pharmaceuticals based on resveratrol-like compounds for the treatment of diabetes are currently in Phase I clinical trials [28].
+<B>1. Improved insulin sensitivity.</B> Resveratrol has been shown as a potent therapeutic for type 2 diabetes [5]. Pharmaceuticals based on resveratrol-like compounds for the treatment of diabetes are currently in Phase I clinical trials [6].
-<B>2. Inhibits carcinogenesis.</B> Resveratrol induces cell death specifically in cancerous cells. This property has been demonstrated for a variety of cancers, including colon [5-7], pancreatic [8], prostate [9,10], breast [11,12], and skin [13,14] cancer. Several ongoing phase I human clinical trials are investigating resveratrol as a cancer therapy [15,16]
+<B>2. Inhibits carcinogenesis.</B> Resveratrol induces cell death specifically in cancerous cells. This property has been demonstrated for a variety of cancers, including colon [7-9], pancreatic [10], prostate [11,12], breast [13,14], and skin [15,16] cancer. Several ongoing phase I human clinical trials are investigating resveratrol as a cancer therapy [17,18]
-<B>3. Extended lifespan.</B>  Resveratrol mimics the effects of caloric restriction in mammals and has been shown to extend lifespans in invertebrates [29,30], anda fish model [31].  In addition, resveratrol reduces the genetic changes  associated with aging in a mammalian mouse model [4,18,32]. PGC-1alpha levels was decreased threefold by induction of genes for oxidative phosphorylation and mitochondrial biogenesis in wt SIRT1 mice but no change in SIRT1(-/-) MEFs [33].
+<B>3. Extended lifespan.</B>  Resveratrol mimics the effects of caloric restriction in mammals and has been shown to extend lifespans in invertebrates [19,20], and a fish model [21].  In addition, resveratrol reduces the genetic changes  associated with aging in a mammalian mouse model [22-24]. PGC-1alpha levels was decreased threefold by induction of genes for oxidative phosphorylation and mitochondrial biogenesis in wt SIRT1 mice but no change in SIRT1(-/-) MEFs [25].
-<B>4. Improved cardiovascular function.</B> Resveratrol exhibits cardioprotective effects, such as the suppression of atherosclerosis, inhibition of platelet aggregation, vasorelaxation promotion, and modulation of triglyceride blood levels [1-4].
+<B>4. Improved cardiovascular function.</B> Resveratrol exhibits cardioprotective effects, such as the suppression of atherosclerosis, inhibition of platelet aggregation, vasorelaxation promotion, and modulation of triglyceride blood levels [22,26-28].
-<B>5. Reduced Neurodegeneration.</B> Mouse models of Alzheimer's and Parkinson's disease have provided evidence that resveratrol functions as a protective agent against degenerative neural diseases[22,23]. In addition, Experiments with rats, mice, and gerbils show that resveratrol administration protects against brain damage following isochemic stroke [24-26].
+<B>5. Reduced Neurodegeneration.</B> Mouse models of Alzheimer's and Parkinson's disease have provided evidence that resveratrol functions as a protective agent against degenerative neural diseases [29,30]. In addition, Experiments with rats, mice, and gerbils show that resveratrol administration protects against brain damage following isochemic stroke [31-33].
-<B>6. Decreases inflammation. </B> NEED A SENTENCE OR TWO SUMMARIZING THESE CITATIONS [18-21].
+<B>6. Decreases inflammation. </B> NEED A SENTENCE OR TWO SUMMARIZING THESE CITATIONS [34,35].
-Our understanding of Resveratrol effects on cellular function is currently too limited to explain the biochemical origin of the diverse pharmacological effects that have been observed to date.
+Unfortunately, our understanding of resveratrol effects on cellular function is currently too limited to explain the biochemical origin of the diverse pharmacological effects that have been observed to date.
 <BR><BR><BR><BR>
@@ Line 53: / Line 53: @@
 [[Image:brewing.jpg|left]]
-One of the best sources of resveratrol is wine, with red wine having concentrations ranging from 0.1 to 14.3mg/L  and white wine having concentrations ranging from <0.1 to 2.1mg/L (Sinclair). Unfortunately, the abundance of resveratrol in this beverage is thought to be too low to allow for all of the health benefits that have been demonstrated in model organisms, beneficial effects have been shown at levels readily achieved in humans [4].
+One of the best sources of resveratrol is wine, with red wine having concentrations ranging from 0.1 to 14.3mg/L  and white wine having concentrations ranging from <0.1 to 2.1mg/L [3]. Unfortunately, the abundance of resveratrol in this beverage is thought to be too low to allow for all of the health benefits that have been demonstrated in model organisms, beneficial effects have been shown at levels readily achieved in humans [4].
-Beer is also expected to contain resveratrol.  Hops that is used to flavor beer contains 0.5 to 1 µg resveratrol/g (Sinclair review), and beer is produced under fermentative conditions, which is likely to prevent the air oxidation and inactivation of resveratrol from the hops. While the levels of resveratrol in beer are less than that of wine, beer represents >85% of all alcoholic beverages consumed in the US (National Institute on Alcohol Abuse and Alcoholism), and thus a better vehicle for widespread delivery of air-sensitive prophylactics like resveratrol.  To increase the level of resveratrol present in beer, we are working to engineer a brewers yeast that synthesizes resveratrol from tyrosine.
+Beer is also expected to contain resveratrol.  Hops that is used to flavor beer contains 0.5 to 1 µg resveratrol/g [3], and beer is produced under fermentative conditions, which is likely to prevent the air oxidation and inactivation of resveratrol from the hops. While the levels of resveratrol in beer are less than that of wine, beer represents >85% of all alcoholic beverages consumed in the US [35], and thus a better vehicle for widespread delivery of air-sensitive prophylactics like resveratrol.  To increase the level of resveratrol present in beer, we are working to engineer a brewers yeast that synthesizes resveratrol from tyrosine.
@@ Line 61: / Line 61: @@
 ==='''References''' ===
-: Samuel SM, et al.   Akt/FOXO3a/SIRT1-mediated cardioprotection by n-tyrosol against ischemic stress in rat in vivo model of myocardial infarction: switching gears toward survival and longevity. J Agric Food Chem. 2008 Oct 22;56(20):9692-8. Epub 2008 Oct 1. PMID: 18826227 [PubMed - in process].
+: Takaoka, M. J. Of the phenolic substances of white hellebore (Veratrum grandiflorum Loes. Fil.) J. Faculty Sci. Hokkaido Imperial University. 1940; 3: 1-16.
-: Hwang JT, et al.   Resveratrol protects ROS-induced cell death by activating AMPK in H9c2 cardiac
+. Hammerschmidt, R. PHYTOALEXINS:What Have We Learned After 60 years. Annu. Rev. Phytopathol. 1999; 37:285–306
-muscle cells.
-Genes Nutr. 2008 Feb;2(4):323-6.
-PMID: 18850225 [PubMed - in process]
-: Gresele P, et al.  Resveratrol, at concentrations attainable with moderate wine consumption,
+.  Baur, J. A. and Sinclair, D. A. Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews Drug Discovery. 2006; 5: 493-506.
-stimulates human platelet nitric oxide production.
-J Nutr. 2008 Sep;138(9):1602-8.
-PMID: 18716157 [PubMed - indexed for MEDLINE]
-: Barger JL, et al.  A low dose of dietary resveratrol partially mimics caloric restriction and
+. Renaud, S. and Gueguen, R. The French Paradox and wine drinking.  Novartis Found. Sympos. 1998; 216:208-217.
-retards aging parameters in mice.
-PLoS ONE. 2008 Jun 4;3(6):e2264.
-PMID: 18523577 [PubMed - indexed for MEDLINE]
-: Juan ME, et al.  Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT-29 human colorectal carcinoma cells.
+. Milne JC, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov 29;450(7170):712-6.
-J Agric Food Chem. 2008 Jun 25;56(12):4813-8. Epub 2008 Jun 4.
-PMID: 18522405 [PubMed - indexed for MEDLINE]
-: Saiko P, et al. Novel resveratrol analogs induce apoptosis and cause cell cycle arrest in HT29
+. http://www.sirtrispharma.com/pipeline-SRT501.html
-human colon cancer cells: inhibition of ribonucleotide reductase activity.
-Oncol Rep. 2008 Jun;19(6):1621-6.
-PMID: 18497974 [PubMed - indexed for MEDLINE]
-: Marel AK, et al. Inhibitory effects of trans-resveratrol analogs molecules on the proliferation and the cell cycle progression of human colon tumoral cells.
+. Juan ME, et al.  Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT-29 human colorectal carcinoma cells. J Agric Food Chem. 2008 Jun 25;56(12):4813-8. Epub 2008 Jun 4.
-Mol Nutr Food Res. 2008 May;52(5):538-48.
-PMID: 18384089 [PubMed - indexed for MEDLINE]
-: Bernhaus A, et al.  Antitumor effects of KITC, a new resveratrol derivative, in AsPC-1 and BxPC-3 human pancreatic carcinoma cells. Invest New Drugs. 2008 Oct 8. [Epub ahead of print]
+. Saiko P, et al. Novel resveratrol analogs induce apoptosis and cause cell cycle arrest in HT29 human colon cancer cells: inhibition of ribonucleotide reductase activity. Oncol Rep. 2008 Jun;19(6):1621-6.
-PMID: 18841326 [PubMed - as supplied by publisher]
-: Seeni A, et al. Suppression of Prostate Cancer Growth by Resveratrol in The Transgenic Rat for Adenocarcinoma of Prostate (TRAP) Model.
+. Marel AK, et al. Inhibitory effects of trans-resveratrol analogs molecules on the proliferation and the cell cycle progression of human colon tumoral cells. Mol Nutr Food Res. 2008 May;52(5):538-48.
-Asian Pac J Cancer Prev. 2008 Jan-Mar;9(1):7-14.
-PMID: 18439064 [PubMed - in process]
-: Horvath Z, et al. Novel resveratrol derivatives induce apoptosis and cause cell cycle arrest in prostate cancer cell lines.
+. Bernhaus A, et al.  Antitumor effects of KITC, a new resveratrol derivative, in AsPC-1 and BxPC-3 human pancreatic carcinoma cells. Invest New Drugs. 2008 Oct 8. [Epub ahead of print]
-Anticancer Res. 2007 Sep-Oct;27(5A):3459-64.
-PMID: 17970095 [PubMed - indexed for MEDLINE]
-: Filomeni G, et al. trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways.
+. Seeni A, et al. Suppression of Prostate Cancer Growth by Resveratrol in The Transgenic Rat for Adenocarcinoma of Prostate (TRAP) Model. Asian Pac J Cancer Prev. 2008 Jan-Mar;9(1):7-14.
-Genes Nutr. 2007 Dec;2(3):295-305. Epub 2007 Oct 18.
-PMID: 18850184 [PubMed - in process]
-: Schlachterman A, et al. Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model.
+. Horvath Z, et al. Novel resveratrol derivatives induce apoptosis and cause cell cycle arrest in prostate cancer cell lines. Anticancer Res. 2007 Sep-Oct;27(5A):3459-64.
-Transl Oncol. 2008 Mar;1(1):19-27.
-PMID: 18607509 [PubMed - in process]
-: Jang M, Cai L, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes.
+. Filomeni G, et al. trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways. Genes Nutr. 2007 Dec;2(3):295-305. Epub 2007 Oct 18.
-Science. 1997 Jan 10;275(5297):218-20.
-PMID: 8985016 [PubMed - indexed for MEDLINE]
-: van Ginkel PR, et al. Resveratrol inhibits uveal melanoma tumor growth via early mitochondrial dysfunction.
+. Schlachterman A, et al. Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model. Transl Oncol. 2008 Mar;1(1):19-27.
-Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1299-306.
-PMID: 18385041 [PubMed - indexed for MEDLINE]
-: http://www.clinicaltrials.gov/ct/show/NCT00256334
+. Jang M, Cai L, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997 Jan 10;275(5297):218-20.
-: http://www.cancer.gov/clinicaltrials/CCUM-2004-0535
+. van Ginkel PR, et al. Resveratrol inhibits uveal melanoma tumor growth via early mitochondrial dysfunction. Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1299-306.
-: Ellen L. Robb, et al. Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD, Biocehm and Biophys Res Comm, 2008
+. http://www.clinicaltrials.gov/ct/show/NCT00256334
-: Kode A, et al. (2007). "Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells". Am J Physiol Lung Cell Mol Physiol.. doi:10.1152 (inactive 2008-06-20). PMID 18162601.
+. http://www.cancer.gov/clinicaltrials/CCUM-2004-0535
-: Venkatachalam K, et al. Resveratrol inhibits high glucose-induced PI3K/Akt/ERK-dependent interleukin-17 expression in primary mouse cardiac fibroblasts.
+. Howitz KT, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003 Sep 11;425(6954):191-6. Epub 2003 Aug 24.
-Am J Physiol Heart Circ Physiol. 2008 May;294(5):H2078-87. Epub 2008 Feb 29.
-PMID: 18310510 [PubMed - indexed for MEDLINE]
-: Zhu J, et al. Anti-inflammatory effect of resveratrol on TNF-alpha-induced MCP-1 expression in adipocytes.
+. Wood JG, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004 Aug 5;430(7000):686-9.
-Biochem Biophys Res Commun. 2008 May 2;369(2):471-7. Epub 2008 Feb 20.
-PMID: 18291098 [PubMed - indexed for MEDLINE]
-: Kennedy A, et al. Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol.
+. Valenzano DR, et al. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol. 2006 Feb 7;16(3):296-300.
-J Lipid Res. 2008 Sep 5. [Epub ahead of print]
-PMID: 18776171 [PubMed - as supplied by publisher]
-: Kim D, et al. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis.
+. Barger JL, et al.  A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS ONE. 2008 Jun 4;3(6):e2264.
-EMBO J. 2007 Jul 11;26(13):3169-79. Epub 2007 Jun 21.
-PMID: 17581637 [PubMed - indexed for MEDLINE]
-: Jin F, et al. Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson's disease in rats.
+. Kode A, et al. (2007). "Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells". Am J Physiol Lung Cell Mol Physiol.
-Eur J Pharmacol. 2008 Oct 10. [Epub ahead of print]
-PMID: 18940189 [PubMed - as supplied by publisher]
-: Sinha K, et al. Protective effect of resveratrol against oxidative stress in middle cerebral
+. Baur JA, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42. Epub 2006 Nov 1.
-artery occlusion model of stroke in rats.
-Life Sci. 2002 Jun 28;71(6):655-65.
-PMID: 12072154 [PubMed - indexed for MEDLINE]
-: Inoue H, et al. Brain protection by resveratrol and fenofibrate against stroke requires
+. M . Lagouge , C . Argmann , Z . Gerhart-Hines , H . Meziane , C . Lerin , F . Daussin , N . Messadeq , J . Milne , P . Lambert , P . Elliott. Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α .  Cell , Volume 127 , Issue 6 , Pages 1109 - 1122
-peroxisome proliferator-activated receptor alpha in mice.
-Neurosci Lett. 2003 Dec 11;352(3):203-6.
-PMID: 14625020 [PubMed - indexed for MEDLINE]
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 |}
 [[Team:Rice_University|SUMMARY]] :::  [[Team:Rice_University/BACKGROUND|BACKGROUND]] :::  [[Team:Rice_University/STRATEGY|STRATEGY]] :::  [[Team:Rice_University/CONSTRUCTS|CONSTRUCTS]] :::  [[Team:Rice_University/RESULTS|RESULTS]] :::  [[Team:Rice_University/CONCLUSIONS|ONGOING WORK]] :::  [[Team:Rice_University/OUR TEAM|OUR TEAM]] :::  [[Team:Rice_University/NOTEBOOK|NOTEBOOK]] :::  [[Team:Rice_University/GALLERY|GALLERY]]
 |}