{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:24:59Z","timestamp":1792272299287,"version":"4.4.0"},"reference-count":149,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Resveratrol (3,4\u2032,5 trihydroxystilbene) is a naturally occurring non-flavonoid polyphenol. It has various pharmacological effects including antioxidant, anti-diabetic, anti-inflammatory and anti-cancer. Many studies have given special attention to different aspects of resveratrol anti-cancer properties and proved its high efficiency in targeting multiple cancer hallmarks. Tumor microenvironment has a critical role in cancer development and progression. Tumor cells coordinate with a cast of normal cells to aid the malignant behavior of cancer. Many cancer supporting players were detected in tumor microenvironment. These players include blood and lymphatic vessels, infiltrating immune cells, stromal fibroblasts and the extracellular matrix. Targeting tumor microenvironment components is a promising strategy in cancer therapy. Resveratrol with its diverse biological activities has the capacity to target tumor microenvironment by manipulating the function of many components surrounding cancer cells. This review summarizes the targets of resveratrol in tumor microenvironment and the mechanisms involved in this targeting. Studies discussed in this review will participate in building a solid ground for researchers to have more insight into the mechanism of action of resveratrol in tumor microenvironment.<\/jats:p>","DOI":"10.3390\/molecules25184282","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T10:22:23Z","timestamp":1600424543000},"page":"4282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Resveratrol and Tumor Microenvironment: Mechanistic Basis and Therapeutic Targets"],"prefix":"10.3390","volume":"25","author":[{"given":"Wamidh H.","family":"Talib","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman 11931-166, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Riyad","family":"Alsayed","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman 11931-166, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1660-7291","authenticated-orcid":false,"given":"Faten","family":"Farhan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Therapeutic, Applied Science Private University, Amman 11931-166, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-7655","authenticated-orcid":false,"given":"Lina T.","family":"Al Kury","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi 144534, UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","unstructured":"World Health Organization (2018). Global Health Observatory, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S185","DOI":"10.1016\/j.semcancer.2015.03.004","article-title":"Immune evasion in cancer: Mechanistic basis and therapeutic strategies","volume":"35","author":"Vinay","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"ref_4","first-page":"1","article-title":"Nutrition and cancer: A review of the evidence for an anti-cancer diet","volume":"21","author":"Donaldson","year":"2004","journal-title":"Nutrition"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.nut.2017.06.015","article-title":"Consumption of garlic and lemon aqueous extracts combination reduces tumor burden by angiogenesis inhibition, apoptosis induction, and immune system modulation","volume":"43","author":"Talib","year":"2017","journal-title":"Nutrition"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1017\/S1368980007668475","article-title":"Diet and cancer risk in Mediterranean countries: Open issues","volume":"9","author":"Vecchia","year":"2006","journal-title":"Public Health Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zheng, J., Yang, B., Huang, T., Yu, Y., Zheng, J., Yang, B., and Huang, T. (2011). Green Tea and Black Tea Consumption and Prostate Cancer Risk: An Exploratory Meta-Analysis of Observational Studies Green Tea and Black Tea Consumption and Prostate Cancer Risk: An Exploratory Meta-Analysis of Observational Studies. Nutr. Cancer, 37\u201341.","DOI":"10.1080\/01635581.2011.570895"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S276","DOI":"10.1016\/j.semcancer.2015.09.007","article-title":"Seminars in Cancer Biology Designing a broad-spectrum integrative approach for cancer prevention and treatment","volume":"35","author":"Block","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2147\/BCTT.S167812","article-title":"Role of curcumin in regulating p53 in breast cancer: An overview of the mechanism of action","volume":"10","author":"Ali","year":"2018","journal-title":"Breast Cancer-Targets Ther."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Falah, R.R., Talib, W.H., and Shbailat, S.J. (2017). Combination of metformin and curcumin targets breast cancer in mice by angiogenesis inhibition, immune system modulation and induction of p53 independent apoptosis. Ther. Adv. Med Oncol., 235\u2013252.","DOI":"10.1177\/1758834016687482"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1016\/j.biopha.2018.08.139","article-title":"Biomedicine & Pharmacotherapy Parthenolide inhibits tumor-promoting effects of nicotine in lung cancer by inducing P53-dependent apoptosis and inhibiting VEGF expression","volume":"107","author":"Talib","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.canlet.2008.03.052","article-title":"Multi-targeted therapy of cancer by genistein","volume":"269","author":"Banerjee","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Talib, W.H. (2017). Regressions of Breast Carcinoma Syngraft Following Treatment with Piperine in Combination with Thymoquinone. Sci. Pharm., 85.","DOI":"10.3390\/scipharm85030027"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hinshaw, D.C., and Shevde, L.A. (2019). The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res., 1\u201311.","DOI":"10.1158\/0008-5472.CAN-18-3962"},{"key":"ref_15","first-page":"272","article-title":"Biological Effects of Resveratrol and Other Constituents of Wine","volume":"52","year":"2003","journal-title":"Ceska Slov. Farm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2012.00141","article-title":"Resveratrol: French paradox revisited","volume":"3","author":"Catalgol","year":"2012","journal-title":"Front. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/mnfr.200800177","article-title":"Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers","volume":"53","author":"Almeida","year":"2009","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.2174\/092986710791556032","article-title":"The Cardiovascular Nutrapharmacology of Resveratrol: Pharmacokinetics, Molecular Mechanisms and Therapeutic Potential","volume":"17","author":"Kroon","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gambini, J., Ingl\u00e9s, M., Olaso, G., Lopez-Grueso, R., Bonet-Costa, V., Gimeno-Mallench, L., Mas-Bargues, C., Abdelaziz, K.M., Gomez-Cabrera, M.C., and Vina, J. (2015). Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans. Oxidative Med. Cell. Longev., 2015.","DOI":"10.1155\/2015\/837042"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1124\/dmd.104.000885","article-title":"High absorption but very low bioavailability of oral resveratrol in humans","volume":"32","author":"Walle","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"ref_21","first-page":"472","article-title":"Metabolism and bioavailability of trans -resveratrol","volume":"49","author":"Wenzel","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3892\/etm.2015.2895","article-title":"Bioavailability and safety study of resveratrol 500 mg tablets in healthy male and female volunteers","volume":"11","author":"Sergides","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/mnfr.200500002","article-title":"Bioavailability of trans-resveratrol from red wine in humans","volume":"49","author":"Vitaglione","year":"2005","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1749-6632.2010.05871.x","article-title":"Transport, stability, and biological activity of resveratrol","volume":"1215","author":"Delmas","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1158\/1055-9965.EPI-07-0022","article-title":"Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent","volume":"16","author":"Boocock","year":"2007","journal-title":"Cancer Epidemiol. Prev. Biomark."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1124\/jpet.102.033340","article-title":"Metabolism and disposition of resveratrol in rats: Extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model","volume":"302","author":"Marier","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bode, L.M., Bunzel, D., Huch, M., Cho, G.-S., Ruhland, D., Bunzel, M., Bub, A., Franz, C.M.A.P., and Kulling, S.E. (2013). In vivo and in vitro metabolism of trans -resveratrol by human gut. Am. J. Clin. Nutr., 295\u2013309.","DOI":"10.3945\/ajcn.112.049379"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0009-9120(02)00397-1","article-title":"Absorption of three wine-related polyphenols in three different matrices by healthy subjects","volume":"36","author":"Goldberg","year":"2003","journal-title":"Clin. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1749-6632.2010.05851.x","article-title":"Resveratrol in cancer management: Where are we and where we go from here? Resveratrol in cancer management: Where are we and where we go from here?","volume":"1215","author":"Ndiaye","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1016\/S0024-3205(03)00096-1","article-title":"Distribution of [14C]-trans-resveratrol, a cancer chemopreventive polyphenol, in mouse tissues after oral administration","volume":"72","author":"Vitrac","year":"2003","journal-title":"Life Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mnfr.201600557","article-title":"Addressing the inter-individual variation in response to consumption of plant food bioactives: Towards a better understanding of their role in healthy aging and cardiometabolic risk reduction","volume":"61","author":"Manach","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1517\/17425255.3.1.93","article-title":"Intestinal UGTs as potential modifiers of pharmacokinetics and biological responses to drugs and xenobiotics","volume":"3","author":"Ritter","year":"2007","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9003","DOI":"10.1158\/0008-5472.CAN-10-2364","article-title":"Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: Safety, pharmacokinetics, and effect on the insulin-like growth factor axis","volume":"70","author":"Brown","year":"2010","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wightman, E.L., Reay, J.L., Haskell, C.F., Williamson, G., Dew, T.P., and Kennedy, D.O. (2014). Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: A randomised, double-blind, placebo-controlled, cross-over investigation. Br. J. Nutr., 203\u2013213.","DOI":"10.1017\/S0007114514000737"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1080\/004982500433282","article-title":"Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural avonoids","volume":"30","author":"Pietrabissa","year":"2000","journal-title":"Xenobiotica"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0076-6879(01)35239-4","article-title":"Absorption of trans-Resveratrol in Rats","volume":"335","author":"Soleas","year":"2001","journal-title":"Method Enzymol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.bbrc.2007.05.224","article-title":"Targeted inhibition of glucuronidation markedly improves drug efficacy in mice\u2014A model","volume":"360","author":"Basu","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hoshino, J., Park, E.-j., Kondratyuk, T.P., Marler, L., Pezzuto, J.M., Breemen, R.B.V., Mo, S., Li, Y., and Cushman, M. (2010). Selective Synthesis and Biological Evaluation of Sulfate-Conjugated Resveratrol Metabolites. Am. Chem. Soc., 5033\u20135043.","DOI":"10.1021\/jm100274c"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1749-6632.2010.05853.x","article-title":"Clinical trials of resveratrol","volume":"1215","author":"Patel","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mnfr.201600686","article-title":"Distribution of trans-resveratrol and its metabolites after acute or sustained administration in mouse heart, brain, and liver","volume":"61","author":"Menet","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.foodchem.2012.03.036","article-title":"Resveratrol metabolites have an antiproliferative effect on intestinal epithelial cancer cells","volume":"134","author":"Storniolo","year":"2012","journal-title":"Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1002\/mnfr.201100772","article-title":"Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes","volume":"56","author":"Lasa","year":"2012","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.phrs.2012.03.009","article-title":"High urinary levels of resveratrol metabolites are associated with a reduction in the prevalence of cardiovascular risk factors in high-risk patients","volume":"65","author":"Lapetra","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/mnfr.200700290","article-title":"Quantification of free and protein-bound trans-resveratrol metabolites and identification of Two novel resveratrol metabolites in human plasma","volume":"52","author":"Burkon","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1021\/jf3001108","article-title":"Distribution of resveratrol metabolites in liver, adipose tissue, and skeletal muscle in rats fed different doses of this polyphenol","volume":"60","author":"MacArulla","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1055\/s-0029-1185533","article-title":"Antitumor activity of resveratrol and its sulfated metabolites against human breast cancer cells","volume":"75","author":"Miksits","year":"2009","journal-title":"Planta Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/00207411.1976.11448721","article-title":"A Comparative Study","volume":"5","author":"Kiev","year":"1976","journal-title":"Int. J. Ment. Health"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"839","DOI":"10.3945\/an.117.016568","article-title":"Cardiovascular and antiobesity effects of resveratrol mediated through the gut microbiota","volume":"8","author":"Bird","year":"2017","journal-title":"Adv. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrc2067","article-title":"The tumour microenvironment as a target for chemoprevention","volume":"7","author":"Albini","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1373\/clinchem.2012.185363","article-title":"Targeting the tumor microenvironment for cancer therapy","volume":"59","author":"Sounni","year":"2013","journal-title":"Clin. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1083\/jcb.201102147","article-title":"The extracellular matrix: A dynamic niche in cancer progression","volume":"196","author":"Lu","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0022-5193(82)90388-5","article-title":"How does the extracellular matrix direct gene expression?","volume":"99","author":"Bissell","year":"1982","journal-title":"J. Theor. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1056\/NEJM198612253152606","article-title":"Tumors: Wounds that do not heal. Similarities between tumor stroma generation and wound healing","volume":"315","author":"Dvorak","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0928-4680(00)00053-5","article-title":"Oxidative stress and apoptosis","volume":"7","author":"Kannan","year":"2000","journal-title":"Pathophysiology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8576","DOI":"10.1128\/MCB.23.23.8576-8585.2003","article-title":"Influence of Induced Reactive Oxygen Species in p53-Mediated Cell Fate Decisions","volume":"23","author":"Macip","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.febslet.2005.12.059","article-title":"Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: A putative mechanism for anticancer properties","volume":"580","author":"Azmi","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3840","DOI":"10.1038\/sj.onc.1203727","article-title":"Redox regulation of p53 during hypoxia","volume":"19","author":"Chandel","year":"2000","journal-title":"Oncogene"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/nrc1455","article-title":"Post-translational modification of p53 in tumorigenesis","volume":"4","author":"Bode","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Luo, H., Yang, A., Schulte, B.A., Wargovich, M.J., and Wang, G.Y. (2013). Resveratrol Induces Premature Senescence in Lung Cancer Cells via ROS-Mediated DNA Damage. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060065"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/cddis.2014.530","article-title":"Resveratrol regulates mitochondrial reactive oxygen species homeostasis through Sirt3 signaling pathway in human vascular endothelial cells","volume":"5","author":"Zhou","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_62","first-page":"1427","article-title":"Resveratrol induced reactive oxygen species and endoplasmic reticulum stress-mediated apoptosis, and cell cycle arrest in the A375SM malignant melanoma cell line","volume":"42","author":"Heo","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ji, S., Zheng, Z., Liu, S., Ren, G., Gao, J., Zhang, Y., and Li, G. (2018). Resveratrol Promotes Oxidative Stress to Drive DLC1 Mediated Cellular Senescence in Cancer Cells, Elsevier Inc.","DOI":"10.1016\/j.yexcr.2018.06.031"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.fct.2016.08.033","article-title":"Cisplatin and resveratrol induce apoptosis and autophagy following oxidative stress in malignant mesothelioma cells","volume":"97","author":"Lee","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1159\/000487576","article-title":"FOXO1, a Potential Therapeutic Target, Regulates Autophagic Flux, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in Human Cholangiocarcinoma QBC939 Cells","volume":"45","author":"Physiology","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/152165400300001471","article-title":"Putative mechanism for anticancer and apoptosis-inducing properties of plant-derived polyphenolic compounds","volume":"50","author":"Hadi","year":"2000","journal-title":"IUBMB Life"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1158\/0008-5472.CAN-11-4094","article-title":"Cellular constituents of immune escape within the tumor microenvironment","volume":"72","author":"Kerkar","year":"2012","journal-title":"Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","article-title":"Macrophage diversity enhances tumor progression and metastasis","volume":"141","author":"Qian","year":"2010","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Weiss, J.M., Subleski, J.J., Wigginton, J.M., and Wiltrout, R.H. (2007). Immunotherapy of cancer by IL-12-based cytokine combinations. Export. Opin., 1705\u20131722.","DOI":"10.1517\/14712598.7.11.1705"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3444","DOI":"10.4049\/jimmunol.146.10.3444","article-title":"IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells","volume":"146","author":"Fiorentino","year":"1991","journal-title":"J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.canlet.2014.05.008","article-title":"Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial\u2013mesenchymal transition in hepatocellular carcinoma","volume":"352","author":"Fan","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"S199","DOI":"10.1016\/j.semcancer.2015.02.007","article-title":"Cancer prevention and therapy through the modulation of the tumor microenvironment","volume":"35","author":"Casey","year":"2015","journal-title":"Semin. Cancer Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1158\/0008-5472.CAN-12-2384","article-title":"Evidence for a role of the PD-1: PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma","volume":"73","author":"Peng","year":"2013","journal-title":"Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cellimm.2016.11.002","article-title":"Resveratrol inhibits lung cancer growth by suppressing M2-like polarization of tumor associated macrophages","volume":"311","author":"Sun","year":"2017","journal-title":"Cell. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1080\/01635581.2016.1158295","article-title":"Resveratrol prevents tumor growth and metastasis by inhibiting lymphangiogenesis and M2 macrophage activation and differentiation in tumor-associated macrophages","volume":"68","author":"Kimura","year":"2016","journal-title":"Nutr. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00262-018-2130-3","article-title":"TriCurin, a synergistic formulation of curcumin, resveratrol, and epicatechin gallate, repolarizes tumor-associated macrophages and triggers an immune response to cause suppression of HPV+ tumors","volume":"67","author":"Mukherjee","year":"2018","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.intimp.2014.07.004","article-title":"Interferon gamma induced by resveratrol analog, HS-1793, reverses the properties of tumor associated macrophages","volume":"22","author":"Jeong","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2788","DOI":"10.4049\/jimmunol.175.5.2788","article-title":"Cutting Edge: Proangiogenic Properties of Alternatively Activated Dendritic Cells","volume":"175","author":"Riboldi","year":"2005","journal-title":"J. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S1471-4906(02)02281-0","article-title":"Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity?","volume":"23","author":"Lutz","year":"2002","journal-title":"Trends Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.it.2012.10.001","article-title":"Indoleamine 2,3 dioxygenase and metabolic control of immune responses","volume":"34","author":"Munn","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1172\/JCI31911","article-title":"Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase","volume":"117","author":"Sharma","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1084\/jem.20020121","article-title":"Tryptophan-derived Catabolites Are Responsible for Inhibition of T and Natural Killer Cell Proliferation Induced by Indoleamine 2,3-Dioxygenase","volume":"196","author":"Frumento","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.imlet.2007.06.001","article-title":"Tumor immune escape mediated by indoleamine 2,3-dioxygenase","volume":"111","author":"Zamanakou","year":"2007","journal-title":"Immunol. Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.bbrc.2012.12.093","article-title":"Resveratrol suppresses tumor progression via the regulation of indoleamine 2,3-dioxygenase","volume":"431","author":"Noh","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.pharep.2016.06.008","article-title":"Resveratrol intake enhances indoleamine-2,3-dioxygenase activity in humans","volume":"68","author":"Gualdoni","year":"2016","journal-title":"Pharmacol. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-07810-w","article-title":"Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis","volume":"9","author":"Zeng","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrc1093","article-title":"Tumorigenesis and the angiogenic switch","volume":"3","author":"Bergers","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nm0603-669","article-title":"The biology of VEGF and its receptors","volume":"9","author":"Ferrara","year":"2003","journal-title":"Nat. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1042\/CS20040370","article-title":"The vascular endothelial growth factor (VEGF)\/VEGF receptor system and its role under physiological and pathological conditions","volume":"109","author":"Takahashi","year":"2005","journal-title":"Clin. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/bs.ircmb.2016.09.007","article-title":"Immunomodulatory activity of VEGF in cancer","volume":"Volume 330","author":"Terme","year":"2017","journal-title":"International Review of Cell and Molecular Biology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/j.1600-065X.2008.00602.x","article-title":"Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells","volume":"222","author":"Marigo","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nature04874","article-title":"Mechanisms of drug inhibition of signalling molecules","volume":"441","author":"English","year":"2006","journal-title":"Nature"},{"key":"ref_93","first-page":"2783","article-title":"Role of resveratrol in prevention and therapy of cancer: Preclinical and clinical studies","volume":"24","author":"Aggarwal","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Hu, W.-H., Chan, G.K.-L., Duan, R., Wang, H.-Y., Kong, X.-P., Dong, T.T.-X., and Tsim, K.W.-K. (2019). Synergy of Ginkgetin and Resveratrol in Suppressing VEGF-Induced Angiogenesis: A Therapy in Treating Colorectal Cancer. Cancers, 11.","DOI":"10.3390\/cancers11121828"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1124\/mol.64.5.1029","article-title":"Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation","volume":"64","author":"Lin","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10456-010-9187-8","article-title":"Anti-angiogenic effects of resveratrol mediated by decreased VEGF and increased TSP1 expression in melanoma-endothelial cell co-culture","volume":"13","author":"Trapp","year":"2010","journal-title":"Angiogenesis"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhang, M., Li, W., Yu, L., and Wu, S. (2014). The suppressive effect of resveratrol on HIF-1\u03b1 and VEGF expression after warm ischemia and reperfusion in rat liver. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109589"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.3892\/mmr.2015.3518","article-title":"Resveratrol suppresses vascular endothelial growth factor secretion via inhibition of CXC-chemokine receptor 4 expression in ARPE-19 cells","volume":"12","author":"Seong","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"102","DOI":"10.4172\/2157-2518.1000102","article-title":"Angioprevention is implicated in resveratrol chemoprevention of experimental hepatocarcinogenesis","volume":"1","author":"Bishayee","year":"2010","journal-title":"J. Carcinog. Mutagen"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5253","DOI":"10.1158\/1078-0432.CCR-03-0588","article-title":"trans-3,4,5\u2032-Trihydroxystibene inhibits hypoxia-inducible factor 1\u03b1 and vascular endothelial growth factor expression in human ovarian cancer cells","volume":"10","author":"Cao","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"188356","DOI":"10.1016\/j.bbcan.2020.188356","article-title":"Fibrosis and cancer: A strained relationship","volume":"1873","author":"Piersma","year":"2020","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nrc1877","article-title":"Fibroblasts in cancer","volume":"6","author":"Kalluri","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.cell.2005.02.034","article-title":"Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1\/CXCL12 secretion","volume":"121","author":"Orimo","year":"2005","journal-title":"Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"6945","DOI":"10.1158\/0008-5472.CAN-10-0785","article-title":"Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness","volume":"70","author":"Giannoni","year":"2010","journal-title":"Cancer Res."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Ha, S.Y., Yeo, S.-Y., Xuan, Y.-h., and Kim, S.-H. (2014). The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099955"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s13277-012-0638-2","article-title":"High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis","volume":"34","author":"Wikberg","year":"2013","journal-title":"Tumor Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1084\/jem.20130110","article-title":"Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia","volume":"210","author":"Tran","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.ccr.2014.04.005","article-title":"Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival","volume":"25","author":"Carstens","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.apsb.2019.11.008","article-title":"Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer","volume":"10","author":"Ramakrishnan","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Yan, B., Cheng, L., Jiang, Z., Chen, K., Zhou, C., Sun, L., Cao, J., Qian, W., Li, J., and Shan, T. (2018). Resveratrol inhibits ROS-promoted activation and glycolysis of pancreatic stellate cells via suppression of miR-21. Oxidative Med. Cell. Longev., 2018.","DOI":"10.1155\/2018\/1346958"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12906-015-0789-y","article-title":"Anti-fibrotic effects of phenolic compounds on pancreatic stellate cells","volume":"15","author":"Lin","year":"2015","journal-title":"BMC Complement. Altern. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.pharmthera.2013.09.004","article-title":"Targeting interleukin-6 in inflammatory autoimmune diseases and cancers","volume":"141","author":"Yao","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrclinonc.2018.8","article-title":"Targeting the IL-6\/JAK\/STAT3 signalling axis in cancer","volume":"15","author":"Johnson","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1158\/1078-0432.CCR-14-2291","article-title":"Interleukin-6 as a therapeutic target","volume":"21","author":"Rossi","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.ctrv.2012.04.007","article-title":"Interleukin-6 signaling pathway in targeted therapy for cancer","volume":"38","author":"Guo","year":"2012","journal-title":"Cancer Treat. Rev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e1093722","DOI":"10.1080\/2162402X.2015.1093722","article-title":"Cytokine patterns in cancer patients: A review of the correlation between interleukin 6 and prognosis","volume":"5","author":"Lippitz","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1002\/ijc.29939","article-title":"CD 90+ stromal cells are the major source of IL-6, which supports cancer stem-like cells and inflammation in colorectal cancer","volume":"138","author":"Huynh","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Lesina, M., W\u00f6rmann, S.M., Neuh\u00f6fer, P., Song, L., and Alg\u00fcl, H. (2014). Interleukin-6 in Inflammatory and Malignant Diseases of the Pancreas, Elsevier. Seminars in Immunology.","DOI":"10.1016\/j.smim.2014.01.002"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.imlet.2016.11.010","article-title":"IL-6 roles\u2013Molecular pathway and clinical implication in pancreatic cancer\u2013A systemic review","volume":"181","author":"Pop","year":"2017","journal-title":"Immunol. Lett."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Swartz, M.A., Iida, N., Roberts, E.W., Sangaletti, S., Wong, M.H., Yull, F.E., Coussens, L.M., and DeClerck, Y.A. (2012). Tumor microenvironment complexity: Emerging roles in cancer therapy. AACR, 2473\u20132480.","DOI":"10.1158\/0008-5472.CAN-12-0122"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Chang, Q., Daly, L., and Bromberg, J. (2014). The IL-6 Feed-forward Loop: A Driver of Tumorigenesis, Elsevier. Seminars in Immunology.","DOI":"10.1016\/j.smim.2014.01.007"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1093\/annonc\/mdv309","article-title":"A phase I trial combining carboplatin\/doxorubicin with tocilizumab, an anti-IL-6R monoclonal antibody, and interferon-\u03b12b in patients with recurrent epithelial ovarian cancer","volume":"26","author":"Dijkgraaf","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"29820","DOI":"10.18632\/oncotarget.25661","article-title":"Systematic literature review of IL-6 as a biomarker or treatment target in patients with gastric, bile duct, pancreatic and colorectal cancer","volume":"9","author":"Vainer","year":"2018","journal-title":"Oncotarget"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"426","DOI":"10.4062\/biomolther.2014.061","article-title":"Resveratrol inhibits IL-6-induced transcriptional activity of AR and STAT3 in human prostate cancer LNCaP-FGC cells","volume":"22","author":"Lee","year":"2014","journal-title":"Biomol. Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.1158\/1078-0432.CCR-09-0640","article-title":"Interleukin-6 regulates androgen synthesis in prostate cancer cells","volume":"15","author":"Chun","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1159\/000277601","article-title":"Pim1 regulates androgen-dependent survival signaling in prostate cancer cells","volume":"84","author":"Zevenhoven","year":"2010","journal-title":"Urol. Int."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.1038\/onc.2012.412","article-title":"Phosphorylation of the androgen receptor by PIM1 in hormone refractory prostate cancer","volume":"32","author":"Ha","year":"2013","journal-title":"Oncogene"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"20635","DOI":"10.1074\/jbc.M709479200","article-title":"The PIM1 kinase is a critical component of a survival pathway activated by docetaxel and promotes survival of docetaxel-treated prostate cancer cells","volume":"283","author":"Zemskova","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrd2060","article-title":"Therapeutic potential of resveratrol: The in vivo evidence","volume":"5","author":"Baur","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.clinbiochem.2006.04.014","article-title":"A comparison of the anticarcinogenic properties of four red wine polyphenols","volume":"39","author":"Soleas","year":"2006","journal-title":"Clin. Biochem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2147\/CMAR.S4544","article-title":"Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer","volume":"1","author":"Nguyen","year":"2009","journal-title":"Cancer Manag. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"7392","DOI":"10.1158\/0008-5472.CAN-10-2027","article-title":"Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients","volume":"70","author":"Patel","year":"2010","journal-title":"Cancer Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1158\/1940-6207.CAPR-11-0148","article-title":"Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases\u2014Safety, pharmacokinetics, and pharmacodynamics","volume":"4","author":"Howells","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/bjh.12154","article-title":"A phase 2 study of SRT 501 (resveratrol) with bortezomib for patients with relapsed and or refractory multiple myeloma","volume":"160","author":"Popat","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1002\/pros.23024","article-title":"A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination","volume":"75","author":"Paller","year":"2015","journal-title":"Prostate"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/01635581.2012.654926","article-title":"Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer","volume":"64","author":"Zhu","year":"2012","journal-title":"Nutr. Cancer"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/ijc.24728","article-title":"Quantitative evaluation of DNA hypermethylation in malignant and benign breast tissue and fluids","volume":"126","author":"Zhu","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_138","first-page":"1306","article-title":"Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors","volume":"60","author":"Masferrer","year":"2000","journal-title":"Cancer Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1210\/er.2008-0028","article-title":"Unraveling insulin-like growth factor binding protein-3 actions in human disease","volume":"30","author":"Feldman","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1002\/pros.23006","article-title":"Resveratrol reduces the levels of circulating androgen precursors but has no effect on, testosterone, dihydrotestosterone, PSA levels or prostate volume. A 4-month randomised trial in middle-aged men","volume":"75","author":"Kjaer","year":"2015","journal-title":"Prostate"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"298ra117","DOI":"10.1126\/scitranslmed.aaa7619","article-title":"Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice","volume":"7","author":"Cai","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.bbadis.2014.11.004","article-title":"Resveratrol and cancer: Challenges for clinical translation","volume":"1852","author":"Singh","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1093\/jnci\/94.8.606","article-title":"Endogenous sex hormones and breast cancer in postmenopausal women: Reanalysis of nine prospective studies","volume":"94","author":"Hormones","year":"2002","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/s12967-014-0223-0","article-title":"A pilot clinical study of resveratrol in postmenopausal women with high body mass index: Effects on systemic sex steroid hormones","volume":"12","author":"Chow","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/S0140-6736(04)16044-3","article-title":"Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: Systematic review and meta-regression analysis","volume":"363","author":"Renehan","year":"2004","journal-title":"Lancet"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1158\/1940-6207.CAPR-09-0155","article-title":"Resveratrol modulates drug-and carcinogen-metabolizing enzymes in a healthy volunteer study","volume":"3","author":"Chow","year":"2010","journal-title":"Cancer Prev. Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/jn\/132.2.257","article-title":"The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful","volume":"132","author":"Juan","year":"2002","journal-title":"J. Nutr."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1093\/toxsci\/kfh263","article-title":"Resveratrol-associated renal toxicity","volume":"82","author":"Crowell","year":"2004","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1016\/j.fct.2011.08.023","article-title":"Subchronic oral toxicity and cardiovascular safety pharmacology studies of resveratrol, a naturally occurring polyphenol with cancer preventive activity","volume":"49","author":"Johnson","year":"2011","journal-title":"Food Chem. Toxicol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/18\/4282\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:11:18Z","timestamp":1760177478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/18\/4282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,18]]},"references-count":149,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["molecules25184282"],"URL":"https:\/\/doi.org\/10.3390\/molecules25184282","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,18]]}}}