Cited by 4,935Sirtuins and Resveratrol in MedicinePhytochemicals and Antioxidant ActivitiesGenomics, phytochemicals, and oxidative stress

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Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes

Jang, Meishiang, Cai, Lining, Udeani, George O., Slowing, Karla V., Thomas, Cathy F., Beecher, Christopher W. W., Fong, Harry H. S., Farnsworth, Norman R., Kinghorn, A. Douglas, Mehta, Rajendra G., Moon, Richard C., Pezzuto, John M.·1997·Science

DOI 10.1126/science.275.5297.218

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Abstract

Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.

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“[7] described the cancer chemopreventive activity of RES, which inhibits cellular events associated with tumour initiation, promotion and progression.”
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“The latter inhibited DNA binding of AP-1 and prevented expression of some AP-1 components in the nucleus of mouse skin cells upon TPA stimulation [89,90].”
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Resveratrol exerts its antiproliferative effect on HepG2 hepatocellular carcinoma cells, by inducing cell cycle arrest, and NOS activation
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Background
Red wines and flavonoids diminishStaphylococcus aureusvirulence with anti-biofilm and anti-hemolytic activities
Cho, H. S., Lee, J., Cho, M. H., & Lee, J. (2014) · Biofouling · doi:10.1080/08927014.2014.991319 · Cited by 115
“Red wines contain > 200 individual phenolic compounds (German & Walzem 2000), and of these, trans-resveratrol has been shown to have anti-aging, anti-carcinogenic, antiinflammatory, and antioxidant properties in humans (Jang et al. 1997; Cottart et al. 2010).”
Background
Aggregation State and p K a Values of ( E )-Resveratrol As Determined by Fluorescence Spectroscopy and UV−Visible Absorption
López-Nicolás, M., & García‐Carmona, F. (2008) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf800843e · Cited by 116
Fighting Cancer with Red Wine? Molecular Mechanisms of Resveratrol
Kraft, T. E., Parisotto, D. A., Schempp, C. M., & Efferth, T. (2009) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408390802248627 · Cited by 116
“antiinitiation activity, anti-promotion activity, and anti-progression activity (Jang et al., 1997).”
Background
The Influence of Energy of Consciousness Healing Treatment on Low Bioavailable Resveratrol in Male Sprague Dawley Rats
Branton, A. (2017) · International Journal of Clinical and Developmental Anatomy · doi:10.11648/j.ijcda.20170303.11 · Cited by 114
“Due to this reason, most parts of the grape plants are used for red wine production during concentration, which made it richer source of resveratrol as compared with the white wine [4, 5].”
Background
Resveratrol analog (Z)‐3,5,4′‐trimethoxystilbene is a potent anti‐mitotic drug inhibiting tubulin polymerization
Schneider, Y., Chabert, P., Stutzmann, J., Coelho, D., Fougerousse, A., Gossé, F., Launay, J., Brouillard, R., & Raul, F. (2003) · International Journal of Cancer · doi:10.1002/ijc.11344 · Cited by 115
Yeast cell factories for fine chemical and API production
Pscheidt, B., & Glieder, A. (2008) · Microbial Cell Factories · doi:10.1186/1475-2859-7-25 · Cited by 116
“[161] used a transgenic yeast strain for the improved production of resveratrol, an antioxidant which was reported to possess cancer chemoprotective properties [162,163].”
Chronic Resveratrol Enhances Endothelium-Dependent Relaxation but Does Not Alter eNOS Levels in Aorta of Spontaneously Hypertensive Rats
Rush, J. W. E., Quadrilatero, J., Levy, A. S., & Ford, R. J. (2007) · Experimental Biology and Medicine · doi:10.3181/00379727-232-2320814 · Cited by 115
Resveratrol increases antioxidant defenses and decreases proinflammatory cytokines in hippocampal astrocyte cultures from newborn, adult and aged Wistar rats
Bellaver, B., de Souza, D. G., Souza, D. O., & Quincozes‐Santos, A. (2014) · Toxicology in Vitro · doi:10.1016/j.tiv.2014.01.006 · Cited by 123
Resveratrol and apoptosis
Lin, H., Tang, H., Davis, F. B., & Davis, P. J. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05846.x · Cited by 116
Electrospray mass spectrometric analysis of 5-hydroperoxy and 5-hydroxyeicosatetraenoic acids generated by lipid peroxidation of red blood cell ghost phospholipids
Hall, L. M., & Murphy, R. C. (1998) · Journal of the American Society for Mass Spectrometry · doi:10.1016/s1044-0305(98)00013-0 · Cited by 115
Toxicogenomics of resveratrol in rat liver
Hebbar, V., Shen, G., Hu, R., Kim, B.-R., Chen, C., Korytko, P. J., Crowell, J. A., LEVINE, B. S., & Kong, A.-N. T. (2005) · Life Sciences · doi:10.1016/j.lfs.2004.10.039 · Cited by 115
Potential Cancer Chemopreventive in Vitro Activities of Monomeric Xanthone Derivatives from the Marine Algicolous Fungus Monodictys putredinis
Krick, A., Kehraus, S., Gerhäuser, C., Klimo, K., Nieger, M., Maier, A., Fiebig, H., Atodiresei, I. L., Raabe, G., Fleischhauer, J., et al. (2007) · Journal of Natural Products · doi:10.1021/np060505o · Cited by 115
A Metabolic Profiling Strategy for the Dissection of Plant Defense against Fungal Pathogens
Aliferis, K. A., Faubert, D., & Jabaji, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111930 · Cited by 115
“In addition to the abovementioned metabolites exhibiting antioxidant activities, other metabolites with well-established scavenging properties synthesized during interactions in pathosystems such as, resveratrol [55], ascorbate [56], ornithine [57], and members of the B6 complex [58] were involved in the soybean-Rhizo…”
Background
Differential inhibition of human cytochrome P450 enzymes by ε-viniferin, the dimer of resveratrol: comparison with resveratrol and polyphenols from alcoholized beverages
Piver, B., Berthou, F., Dréano, Y., & Lucas, D. (2003) · Life Sciences · doi:10.1016/s0024-3205(03)00420-x · Cited by 115
Bioactivity of Grape Chemicals for Human Health
Iriti, M., & Faoro, F. (2009) · Natural Product Communications · doi:10.1177/1934578x0900400502 · Cited by 119
Differential effects of resveratrol and its naturally occurring methylether analogs on cell cycle and apoptosis in human androgen‐responsive LNCaP cancer cells
Wang, T. T. Y., Schoene, N. W., Kim, Y. S., Mizuno, C. S., & Rimando, A. M. (2010) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200900143 · Cited by 115
Inhibition of protein kinase C by resveratrol
Slater, S. J., Seiz, J. L., Cook, A. C., Stagliano, B. A., & Buzas, C. J. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(02)00214-4 · Cited by 115
Metabolic Engineering of Yeast and Plants for the Production of the Biologically Active Hydroxystilbene, Resveratrol
Jeandet, P., Delaunois, B., Aziz, A., Donnez, D., Vasserot, Y., Cordelier, S., & Courot, É. (2012) · BioMed Research International · doi:10.1155/2012/579089 · Cited by 120
“Since the pioneering work of the group of Pezzuto [33], affording for the very first time evidence for the cancer chemoprotective activity of resveratrol on HL-60 and Hepa 1clc7 cells, many other models of human cancers were used, confirming these findings.”
Background
Role of maspin in cancer
Berardi, R., Morgese, F., Onofri, A., Mazzanti, P., Pistelli, M., Ballatore, Z., Savini, A., Lisa, M. D., Caramanti, M., Rinaldi, S., et al. (2013) · Clinical and Translational Medicine · doi:10.1186/2001-1326-2-8 · Cited by 122
“For example, resveratrol inhibits cell proliferation, induces apoptosis of human prostate carcinoma and acute lymphoblastic leukemia cells and increases maspin levels through Akt pathway [159-163].”
Background
Natural products: a hope for glioblastoma patients
Vengoji, R., Macha, M. A., Batra, S. K., & Shonka, N. (2018) · Oncotarget · doi:10.18632/oncotarget.25175 · Cited by 117
“Resveratrol is a potent anti-oxidant found in grapes, peanuts and mulberries [31] with known anti-tumor activity [31].”
Background
Inhibitory effects of brown algal phlorotannins on secretory phospholipase A2s, lipoxygenases and cyclooxygenases
Shibata, T., Nagayama, K., Tanaka, R., Yamaguchi, K., & Nakamura, T. (2003) · Journal of Applied Phycology · doi:10.1023/a:1022972221002 · Cited by 114
“Resveratrol is well known to be a COX-1 inhibitor (Jang et al. 1997) and showed 98.8% inhibition of COX-1 at 100 µM in this study.”
BackgroundInfluential
Resveratrol selectively inhibits leukemia cells: a prospective agent for ex vivo bone marrow purging
Gautam, S. C., Xu, Y., Dumaguin, M., Janakiraman, N., & Chapman, R. (2000) · Bone Marrow Transplantation · doi:10.1038/sj.bmt.1702189 · Cited by 114
Synergistic antioxidant effect of catechin and malvidin 3-glucoside on free radical-initiated peroxidation of linoleic acid in micelles.
Rossetto, M., Vanzani, P., Mattivi, F., Lunelli, M., Scarpa, M., & Rigo, A. (2002) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00561-1 · Cited by 105
Post-Transcriptional Regulation of Melanin Biosynthetic Enzymes by cAMP and Resveratrol in Human Melanocytes
Newton, R. A., Cook, A. L., Roberts, D. W., Leonard, J. H., & Sturm, R. A. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700840 · Cited by 114
“Interest in this compound has shown a marked renewal in recent years, being initially triggered by its identification as a chemotherapeutic agent for skin cancer (Jang et al., 1997) and subsequently from its protective effects against heart disease and ability to extend lifespans of lower organisms (reviewed in Baur a…”
Background
Effects of selected food factors with chemopreventive properties on combined lipopolysaccharide- and interferon-γ-induced IκB degradation in RAW264.7 macrophages
Murakami, A., Matsumoto, K., Koshimįzu, K., & Ohigashi, H. (2003) · Cancer Letters · doi:10.1016/s0304-3835(03)00058-2 · Cited by 114
Pinostrobin from Honey and Thai Ginger (Boesenbergia pandurata): A Potent Flavonoid Inducer of Mammalian Phase 2 Chemoprotective and Antioxidant Enzymes
Fahey, J. W., & Stephenson, K. K. (2002) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf025692k · Cited by 114
Resveratrol-loaded polymeric nanoparticles suppress glucose metabolism and tumor growth in vitro and in vivo
Jung, K., Lee, J. H., Park, J. W., Quach, C. H. T., Moon, S. H., Cho, Y. S., & Lee, K.-H. (2014) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2014.11.049 · Cited by 113
Resveratrol Oligomers for the Prevention and Treatment of Cancers
Xue, Y., Di, J., Luo, Y., Cheng, K., Wei, X., & Shi, Z. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/765832 · Cited by 113
“Loes [6], found in at least 72 plant species including 12 families and 31 genera [7], and widely exist in edible foods and beverages such as mulberries, peanuts, grapes, and red wine [8].”
Background
Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation
Maugeri, A., Barchitta, M., Mazzone, M. G., Giuliano, F., Basile, G., & Agodi, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19072118 · Cited by 119
“In fact, resveratrol stimulates SIRT1 activity through allosteric interaction and increases SIRT1 affinity for both NAD+ and the acetylated substrate [37,38].”
Background
Deactylation by SIRT1 enables liquid–liquid phase separation of IRF3/IRF7 in innate antiviral immunity
Qin, Z., Fang, X., Sun, W., Ma, Z., Dai, T., Wang, S., Zong, Z., Huang, H., Ru, H., Lu, H., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01269-0 · Cited by 113
Biological function of resveratrol and its application in animal production: a review
Meng, Q., Li, J., Wang, C., & Shan, A. (2023) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-022-00822-z · Cited by 116
Less-known botanical cosmeceuticals
Baumann, L. (2007) · Dermatologic Therapy · doi:10.1111/j.1529-8019.2007.00147.x · Cited by 114
Resveratrol inhibition of varicella-zoster virus replication in vitro
Docherty, J. J., Sweet, T. J., Bailey, E. B., Faith, S. A., & Booth, T. D. (2006) · Antiviral Research · doi:10.1016/j.antiviral.2006.07.004 · Cited by 113
Cellular Uptake and Efflux oftrans-Piceid and Its Aglyconetrans-Resveratrol on the Apical Membrane of Human Intestinal Caco-2 Cells
Henry-Vitrac, C., Vitrac, X., Décendit, A., Ennamany, R., Krisa, S., & Mérillon, J. (2005) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf048909e · Cited by 113
Optimisation of sample preparation for the determination of trans-resveratrol and other polyphenolic compounds in wines by high performance liquid chromatography
Malovaná, S., Montelongo, F. J. G., Pérez, J. P., & Rodríguez‐Delgado, M. Á. (2001) · Analytica Chimica Acta · doi:10.1016/s0003-2670(00)01231-9 · Cited by 110
Colorectal cancer chemoprevention by trans-resveratrol
Juan, M. E., Alfaras, I., & Planas, J. M. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.03.010 · Cited by 113
“In 1997, trans-resveratrol was found to inhibit cellular events associated with the three stages of cancer development, namely, initiation, promotion and progression [5].”
Background
Grape seed and red wine polyphenol extracts inhibit cellular cholesterol uptake, cell proliferation, and 5-lipoxygenase activity
Leifert, W. R., & Abeywardena, M. Y. (2008) · Nutrition Research · doi:10.1016/j.nutres.2008.09.001 · Cited by 112
“Stilbenes, anthocyanins, and procyanidins from grape skin, seeds, and wines have been shown to exhibit anti-inflammatory and antioxidant activities [36-38], and there has been a positive correlation between antioxidant activity and the total phenolic content of samples [39].”
Background
Dietary polyphenols: Focus on resveratrol, a promising agent in the prevention of cardiovascular diseases and control of glucose homeostasis
Borriello, A., Cucciolla, V., Ragione, F. D., & Galletti, P. (2010) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2010.07.004 · Cited by 115
“An analysis of PubMed database indicates that the number of studies on resveratrol has increased extraordinarily since 1997, when the anticancer effect of the molecule was reported for the first time [5].”
Dihydroxyphenylethanol induces apoptosis by activating serine/threonine protein phosphatase PP2A and promotes the endoplasmic reticulum stress response in human colon carcinoma cells
Guichard, C. (2006) · Carcinogenesis · doi:10.1093/carcin/bgl009 · Cited by 111
“Resveratrol, another polyphenol found in grape skins, has also been shown to induce upregulation of p21Cip1/WAF1, p53 and Bax and concomitant downregulation of cyclins D1 and E and anti-apoptotic Bcl-2, leading to arrest of the cell cycle in various in vitro and in vivo models ( 18 ).”
Background
Hepatoprotective and Anti-fibrotic Agents: It's Time to Take the Next Step
Weiskirchen, R. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00303 · Cited by 112
Stilbene Levels in Grape Cane of Different Cultivars in Southern Chile: Determination by HPLC-DAD-MS/MS Method
Vergara, C., von Baer, D., Mardones, C., Wilkens, A., Wernekinck, K., Damm, A., Macke, S., Gorena, T., & Winterhalter, P. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf204482c · Cited by 113
Host–Guest Interaction Study of Resveratrol With Natural and Modified Cyclodextrins
Bertacche, V., Lorenzi, N., Nava, D., Pini, E., & Sinico, C. (2006) · Journal of Inclusion Phenomena and Macrocyclic Chemistry · doi:10.1007/s10847-006-9047-8 · Cited by 112
Oligostilbenoids in stem bark of Vatica rassak
Tanaka, T., Ito, T., Nakaya, K., Iinuma, M., & Riswan, S. (2000) · Phytochemistry · doi:10.1016/s0031-9422(00)00026-1 · Cited by 112

Authors: Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., Thomas, C. F., Beecher, C. W. W., Fong, H. H. S., Farnsworth, N. R., Kinghorn, A. D., Mehta, R. G., Moon, R. C., & Pezzuto, J. M.
Affiliations: University of Illinois Chicago (US)
Universidad Complutense de Madrid (ES)
M. Jang, L. Cai, C. W. W. Beecher, H. H. S. Fong, N. R. Farnsworth, A. D. Kinghorn, J. M. Pezzuto, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Corresponding author: Cai, Lining
Pezzuto, John M.
ORCID: Udeani, George O.
Slowing, Karla V.
Kinghorn, A. Douglas
Mehta, Rajendra G.
Pezzuto, John M.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1997-01-10
Volume: 275
Issue: 5297
Pages: 218-220
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.275.5297.218
OpenAlex: W2151089147
Cited by: 4,935
References: 33
Citations by year: 2026: 45 · 2025: 75 · 2024: 105 · 2023: 95 · 2022: 148 · 2021: 166 · 2020: 179 · 2019: 168 · 2018: 181 · 2017: 202 · 2016: 179 · 2015: 222 · 2014: 225 · 2013: 264 · 2012: 252
FWCI: 96.50
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
Funders: National Cancer Institute (P01CA048112)
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords: resveratrol, chemoprevention, phytoalexins, grapes, antioxidant activity, antimutagenic activity, phase II enzymes, anti-inflammatory activity, cyclooxygenase inhibition, mammary carcinogenesis, precancerous lesions

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Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes

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