| RESVERATROL Cancers |
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other website or blog.
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Can resveratrol be an anti-cancer agent?
As early as 1997, researchers from University of Illinois at Chicago have proposed to
use resveratrol as a cancer-preventive agent. [1] They based on the facts (at that
time) that resveratrol was shown to have anti-cancer activities in assays representing
three major stages of carcinogenesis. At that time, resveratrol was already known as
an antioxidant and antimutagen and to be able to induce phase II drug-metabolizing
enzymes (anti-initiation activity). A few animal studies supported their speculation that
resveratrol could be a candidate to treat cancers. Since then, there were many
animal studies about how to use resveratrol lower the risk of having cancers or use
resveratrol as an adjuvant agent for chemotherapies. In this article, I'm going to
highlight a few interesting studies:
Observation (Epidemiological Studies)
Trans-resveratrol (RSVL; 3,4',5-trihydroxystilbene), a natural compound found in
grapes, berries, peanuts and red wine exerts certain anticancer roles in different
human cancer types. Several epidemiological studies have revealed that resveratrol
is probably one of the active ingredients of wine responsible for its health benefits
such as prevention of vaso-coronary diseases and cancer. Resveratrol acts on the
process of carcinogenesis by affecting the three phases: tumor initiation, promotion
and progression phases and suppresses the final steps of carcinogenesis, i.e.
angiogenesis and metastasis. It is also able to activate apoptosis, to arrest the cell
cycle or to inhibit kinase pathways. [2]
Intensifying Anti-cancer Agents
Resveratrol adds to the growth inhibitory/anticancer activity of cisplatin and
doxorubicin in vitro and protects against doxorubicin-induced cardiac toxicity both in
vitro and in mice. [3]
Endometrial Cancer/ Human Uterine Cancer Cells
Endometrial cancer is the fourth most prominent cancer among all feminine cancers
in the Western world. At the molecular level, resveratrol has been reported to inhibit
cyclooxygenase (COX) expression and/or activity; in endometrial cancer cells, COX-2
is overexpressed and confers cellular resistance to apoptosis. Researchers from
Université du Québec found that high-doses of resveratrol triggered apoptosis in five
out of six uterine cancer cell lines. [4]
Colon Cancer / HT-29 Colon Cancer Cells
Resveratrol exhibited a variety of molecular events in etoposide-based combination
therapy in HT-29 colon cancer cells including the activation of adenosine
monophosphate (AMP)-activated protein kinase, inhibition of cell growth, induction of
apoptosis, and reactive oxygen species (ROS) generation. [5]
Breast Cancer / Human Breast Cancer Cells
Researchers from Kuwait University, found resveratrol-induced growth inhibition in
T47D human breast cancer cells was caused by apoptosis in a cell study.
Resveratrol-induced apoptosis is associated with the activation of the p53 in a dose-
and a time-dependent manner. [6]
Researchers from China Medical University, Taiwan, found resveratrol significantly
inhibited growth factor heregulin-beta1 (HRG-beta1)-mediated Matrix
metalloproteinase (MMP-9) expression in human breast cancer cells. Resveratrol
significantly suppressed HRG-beta1-mediated phosphorylation of ERK1/2 and
invasion of breast cancer cells. [8]
Prostate Cancer / Mouse
Researchers from University of Alabama at Birmingham fed transgenic
Adenocarcinoma Mouse Prostate males with resveratrol (625 mg resveratrol per kg
AIN-76A diet) or phytoestrogen-free, control diet (AIN-76A). They found resveratrol in
the diet significantly reduced the incidence of poorly differentiated prostatic
adenocarcinoma by 7.7-fold. [9]
Lung Cancer / Microarray
Researchers from IIT Research Institute showed resveratrol as a potent inhibitor of
A549 lung cancer cell growth based on a microarray gene expression study. [10]
Clinical Study in Human
A phase I study of oral resveratrol (single doses of 0.5, 1, 2.5, or 5 g) was conducted
by Leicester University, UK, in 10 healthy volunteers per dose level. Resveratrol and
six metabolites were recovered from plasma and urine. Peak plasma levels of
resveratrol at the highest dose were 539 +/- 384 ng/mL (2.4 micromol/L), which
occurred 1.5 h post-dose. Cancer preventive effects of resveratrol in cells in vitro
require levels of at least 5 micromol/L. The results suggest that consumption of
high-dose resveratrol might be insufficient to elicit systemic levels commensurate with
cancer preventive efficacy. [7]
Conclusion
Please, note that I listed only a few studies here. There are lots more studies about
the anti-cancer activities of resveratrol. But, most of them were done in vitro and in
animal models. It is not sure if resveratrol works the same way in human. Though the
Phase I Study (above) indicates the amount of resveratrol absorbed in the blood
stream may not be sufficient to lower the risk of cancer. However, proper formulation
may overcome the solubility or absorption issues.
Resveratrol Side Effects and Benefits
Resveratrol Cream
Resveratrol Arthritis
Resveratrol Diabetes
Does grape seed extract lower bad cholesterol?
Reference:
[1] Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH,
Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM. Cancer
chemopreventive activity of resveratrol, a natural product derived from
grapes. Science. 1997 Jan 10;275(5297):218-20. [2] Delmas D, Lançon A, Colin D,
Jannin B, Latruffe N. Resveratrol as a chemopreventive agent: a promising molecule
for fighting cancer. Curr Drug Targets. 2006 Apr;7(4):423-42. [3] Rezk YA, Balulad
SS, Keller RS, Bennett JA. Use of resveratrol to improve the effectiveness of cisplatin
and doxorubicin: study in human gynecologic cancer cell lines and in rodent heart.
Am J Obstet Gynecol. 2006 May;194(5):e23-6. Epub 2006 Apr 21. [4] Sexton E, Van
Themsche C, LeBlanc K, Parent S, Lemoine P, Asselin E. Resveratrol interferes with
AKT activity and triggers apoptosis in human uterine cancer cells. Mol Cancer. 2006
Oct 17;5:45. [5] Hwang JT, Kwak DW, Lin SK, Kim HM, Kim YM, Park OJ. Resveratrol
induces apoptosis in chemoresistant cancer cells via modulation of AMPK signaling
pathway. Ann N Y Acad Sci. 2007 Jan;1095:441-8. [6] Alkhalaf M.
Resveratrol-induced apoptosis is associated with activation of p53 and inhibition of
protein translation in T47D human breast cancer cells. Pharmacology.
2007;80(2-3):134-43. Epub 2007 May 29. [7] Boocock DJ, Faust GE, Patel KR,
Schinas AM, Brown VA, Ducharme MP, Booth TD,
Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE. Phase I dose escalation
pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer
chemopreventive agent. Cancer Epidemiol Biomarkers Prev. 2007
Jun;16(6):1246-52. [8] Tang FY, Chiang EP, Sun YC. Resveratrol inhibits
heregulin-beta1-mediated matrix metalloproteinase-9 expression and cell invasion in
human breast cancer cells. J Nutr Biochem. 2008 May;19(5):287-94. Epub 2007 Jul
24. [9] Harper CE, Patel BB, Wang J, Arabshahi A, Eltoum IA, Lamartiniere CA.
Resveratrol suppresses prostate cancer progression in transgenic mice.
Carcinogenesis. 2007 Sep;28(9):1946-53. Epub 2007 Aug 3. [10] Whyte L, Huang
YY, Torres K, Mehta RG. Molecular mechanisms of resveratrol action in lung cancer
cells using dual protein and microarray analyses. Cancer Res. 2007 Dec
15;67(24):12007-17.
As early as 1997, researchers from University of Illinois at Chicago have proposed to
use resveratrol as a cancer-preventive agent. [1] They based on the facts (at that
time) that resveratrol was shown to have anti-cancer activities in assays representing
three major stages of carcinogenesis. At that time, resveratrol was already known as
an antioxidant and antimutagen and to be able to induce phase II drug-metabolizing
enzymes (anti-initiation activity). A few animal studies supported their speculation that
resveratrol could be a candidate to treat cancers. Since then, there were many
animal studies about how to use resveratrol lower the risk of having cancers or use
resveratrol as an adjuvant agent for chemotherapies. In this article, I'm going to
highlight a few interesting studies:
Observation (Epidemiological Studies)
Trans-resveratrol (RSVL; 3,4',5-trihydroxystilbene), a natural compound found in
grapes, berries, peanuts and red wine exerts certain anticancer roles in different
human cancer types. Several epidemiological studies have revealed that resveratrol
is probably one of the active ingredients of wine responsible for its health benefits
such as prevention of vaso-coronary diseases and cancer. Resveratrol acts on the
process of carcinogenesis by affecting the three phases: tumor initiation, promotion
and progression phases and suppresses the final steps of carcinogenesis, i.e.
angiogenesis and metastasis. It is also able to activate apoptosis, to arrest the cell
cycle or to inhibit kinase pathways. [2]
Intensifying Anti-cancer Agents
Resveratrol adds to the growth inhibitory/anticancer activity of cisplatin and
doxorubicin in vitro and protects against doxorubicin-induced cardiac toxicity both in
vitro and in mice. [3]
Endometrial Cancer/ Human Uterine Cancer Cells
Endometrial cancer is the fourth most prominent cancer among all feminine cancers
in the Western world. At the molecular level, resveratrol has been reported to inhibit
cyclooxygenase (COX) expression and/or activity; in endometrial cancer cells, COX-2
is overexpressed and confers cellular resistance to apoptosis. Researchers from
Université du Québec found that high-doses of resveratrol triggered apoptosis in five
out of six uterine cancer cell lines. [4]
Colon Cancer / HT-29 Colon Cancer Cells
Resveratrol exhibited a variety of molecular events in etoposide-based combination
therapy in HT-29 colon cancer cells including the activation of adenosine
monophosphate (AMP)-activated protein kinase, inhibition of cell growth, induction of
apoptosis, and reactive oxygen species (ROS) generation. [5]
Breast Cancer / Human Breast Cancer Cells
Researchers from Kuwait University, found resveratrol-induced growth inhibition in
T47D human breast cancer cells was caused by apoptosis in a cell study.
Resveratrol-induced apoptosis is associated with the activation of the p53 in a dose-
and a time-dependent manner. [6]
Researchers from China Medical University, Taiwan, found resveratrol significantly
inhibited growth factor heregulin-beta1 (HRG-beta1)-mediated Matrix
metalloproteinase (MMP-9) expression in human breast cancer cells. Resveratrol
significantly suppressed HRG-beta1-mediated phosphorylation of ERK1/2 and
invasion of breast cancer cells. [8]
Prostate Cancer / Mouse
Researchers from University of Alabama at Birmingham fed transgenic
Adenocarcinoma Mouse Prostate males with resveratrol (625 mg resveratrol per kg
AIN-76A diet) or phytoestrogen-free, control diet (AIN-76A). They found resveratrol in
the diet significantly reduced the incidence of poorly differentiated prostatic
adenocarcinoma by 7.7-fold. [9]
Lung Cancer / Microarray
Researchers from IIT Research Institute showed resveratrol as a potent inhibitor of
A549 lung cancer cell growth based on a microarray gene expression study. [10]
Clinical Study in Human
A phase I study of oral resveratrol (single doses of 0.5, 1, 2.5, or 5 g) was conducted
by Leicester University, UK, in 10 healthy volunteers per dose level. Resveratrol and
six metabolites were recovered from plasma and urine. Peak plasma levels of
resveratrol at the highest dose were 539 +/- 384 ng/mL (2.4 micromol/L), which
occurred 1.5 h post-dose. Cancer preventive effects of resveratrol in cells in vitro
require levels of at least 5 micromol/L. The results suggest that consumption of
high-dose resveratrol might be insufficient to elicit systemic levels commensurate with
cancer preventive efficacy. [7]
Conclusion
Please, note that I listed only a few studies here. There are lots more studies about
the anti-cancer activities of resveratrol. But, most of them were done in vitro and in
animal models. It is not sure if resveratrol works the same way in human. Though the
Phase I Study (above) indicates the amount of resveratrol absorbed in the blood
stream may not be sufficient to lower the risk of cancer. However, proper formulation
may overcome the solubility or absorption issues.
Resveratrol Side Effects and Benefits
Resveratrol Cream
Resveratrol Arthritis
Resveratrol Diabetes
Does grape seed extract lower bad cholesterol?
Reference:
[1] Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH,
Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM. Cancer
chemopreventive activity of resveratrol, a natural product derived from
grapes. Science. 1997 Jan 10;275(5297):218-20. [2] Delmas D, Lançon A, Colin D,
Jannin B, Latruffe N. Resveratrol as a chemopreventive agent: a promising molecule
for fighting cancer. Curr Drug Targets. 2006 Apr;7(4):423-42. [3] Rezk YA, Balulad
SS, Keller RS, Bennett JA. Use of resveratrol to improve the effectiveness of cisplatin
and doxorubicin: study in human gynecologic cancer cell lines and in rodent heart.
Am J Obstet Gynecol. 2006 May;194(5):e23-6. Epub 2006 Apr 21. [4] Sexton E, Van
Themsche C, LeBlanc K, Parent S, Lemoine P, Asselin E. Resveratrol interferes with
AKT activity and triggers apoptosis in human uterine cancer cells. Mol Cancer. 2006
Oct 17;5:45. [5] Hwang JT, Kwak DW, Lin SK, Kim HM, Kim YM, Park OJ. Resveratrol
induces apoptosis in chemoresistant cancer cells via modulation of AMPK signaling
pathway. Ann N Y Acad Sci. 2007 Jan;1095:441-8. [6] Alkhalaf M.
Resveratrol-induced apoptosis is associated with activation of p53 and inhibition of
protein translation in T47D human breast cancer cells. Pharmacology.
2007;80(2-3):134-43. Epub 2007 May 29. [7] Boocock DJ, Faust GE, Patel KR,
Schinas AM, Brown VA, Ducharme MP, Booth TD,
Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE. Phase I dose escalation
pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer
chemopreventive agent. Cancer Epidemiol Biomarkers Prev. 2007
Jun;16(6):1246-52. [8] Tang FY, Chiang EP, Sun YC. Resveratrol inhibits
heregulin-beta1-mediated matrix metalloproteinase-9 expression and cell invasion in
human breast cancer cells. J Nutr Biochem. 2008 May;19(5):287-94. Epub 2007 Jul
24. [9] Harper CE, Patel BB, Wang J, Arabshahi A, Eltoum IA, Lamartiniere CA.
Resveratrol suppresses prostate cancer progression in transgenic mice.
Carcinogenesis. 2007 Sep;28(9):1946-53. Epub 2007 Aug 3. [10] Whyte L, Huang
YY, Torres K, Mehta RG. Molecular mechanisms of resveratrol action in lung cancer
cells using dual protein and microarray analyses. Cancer Res. 2007 Dec
15;67(24):12007-17.