The Therapeutic Potential of Resveratrol in Gliomas

Seidu A. Richard


Resveratrol (RSV) is found in most human foods especially fruits such as grapes, peanuts, strawberry, blueberry, cranberry, mulberry, lingberry, sparkleberry, bilberry and in flowers as well as leaves like butterfly orchid tree, eucalyptus, spruce, lily, gnetum and so many others. Functionally, RSV has the propensity to safeguard DNA as well as the induction of DNA repair. RSV is precipitously metabolized in the liver via phase-II detoxification enzymes leading to its principal urine excretion. RSV steered growth inhibition, induction of apoptosis and G0/G1-phase cell cycle arrest in an experiment involving glioma cells. RVS can block the triggering of signal transducer and activator of transcription (STAT3) signaling of glioma cells. RSV subdues STAT3 signaling via the inhibition of SRC or Janus kinase (JAK2) induction, thereby inducing growth inhibitory and apoptotic properties. RSV explicitly blocks both COX-1 and COX-2 in-vitro. In the cancer inflammatory milieu, the blockade effects of RSV on NF-κB could also lead to the blockade of TNF-α resulting in inhibition of cancer advancement as well as metastasis. Individually, RSV has proven to very potent in glioma cells. It is able to down-regulate glioma angiogenesis as well as metastasis. In combination with other agents, RVS augment its potency in glioma. RVS is able to cross the blood brain barrier (BBB) via gap junctions making it very efficient central nervous system medication. RVS after oral administration peaks in the blood stream after one hour meaning it acts very fast. This review focuses on the neuropharmacological role of RVS in glioma.


Resveratrol, Glioma, Therapeutic, Angiogenesis, Metastasis, Grapes

Full Text:



Aggarwal, B.B.; Bhardwaj, A.; Aggarwal, R.S.; Seeram, N.P.; Shishodia, S.; Takada, Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer research, 2004, 24(5A), 2783-2840.

Ahn, J.-H.; Choi, Y.S.; Choi, J.-H. Leptin promotes human endometriotic cell migration and invasion by up-regulating MMP-2 through the JAK2/STAT3 signaling pathway. MHR: Basic science of reproductive medicine, 2015, 21(10), 792-802.

Alberdi, E.; Sánchez-Gómez, M.V.; Matute, C. Calcium and glial cell death. Cell calcium, 2005, 38(3-4), 417-425.

Anastasiadis, P.Z.; Jiang, H.; Bezin, L.; Kuhn, D.M.; Levine, R.A. Tetrahydrobiopterin enhances apoptotic PC12 cell death following withdrawal of trophic support. Journal of Biological Chemistry, 2001, 276(12), 9050-9058.

Balkwill, F. TNF-α in promotion and progression of cancer. Cancer and Metastasis Reviews, 2006, 25(3), 409.

Bao, S.; Wu, Q.; McLendon, R.E.; Hao, Y.; Shi, Q.; Hjelmeland, A.B.; Dewhirst, M.W.; Bigner, D.D.; Rich, J.N. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature, 2006, 444(7120), 756.

Baur, J.A.; Sinclair, D.A. Therapeutic potential of resveratrol: the in vivo evidence. Nature reviews Drug discovery, 2006, 5(6), 493.

Bertelli, A.; Bertelli, A.; Gozzini, A.; Giovannini, L. Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs under experimental and clinical research, 1998, 24(3), 133-138.

Bertl, E.; Bartsch, H.; Gerhäuser, C. Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention. Molecular cancer therapeutics, 2006, 5(3), 575-585.

Beskow, C.; Skikuniene, J.; Holgersson, Å.; Nilsson, B.; Lewensohn, R.; Kanter, L.; Viktorsson, K. Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86. British journal of cancer, 2009, 101(5), 816.

Brantley, E.C.; Benveniste, E.N. Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas. Molecular Cancer Research, 2008, 6(5), 675-684.

Brem, S.; Cotran, R.; Folkman, J. Tumor angiogenesis: a quantitative method for histologic grading. Journal of the National Cancer Institute, 1972, 48(2), 347-356.

Bromberg, J. Stat proteins and oncogenesis. The Journal of clinical investigation, 2002, 109(9), 1139-1142.

Bromberg, J.; Darnell, J.E. The role of STATs in transcriptional control and their impact on cellular function. Oncogene, 2000, 19(21), 2468.

Brown, L.; Kroon, P.A.; Das, D.K.; Das, S.; Tosaki, A.; Chan, V.; Singer, M.V.; Feick, P. The biological responses to resveratrol and other polyphenols from alcoholic beverages. Alcoholism: Clinical and Experimental Research, 2009, 33(9), 1513-1523.

Castagne, V.; Gautschi, M.; Lefevre, K.; Posada, A.; Clarke, P.G. Relationships between neuronal death and the cellular redox status. Focus on the developing nervous system. Progress in neurobiology, 1999, 59(4), 397-423.

Chakraborty, S.; Roy, M.; Bhattacharya, R.K. Prevention and repair of DNA damage by selected phytochemicals as measured by single cell gel electrophoresis. Journal of environmental pathology, toxicology and oncology, 2004, 23(3).

Chang, H.-C.; Tai, Y.-T.; Cherng, Y.-G.; Lin, J.-W.; Liu, S.-H.; Chen, T.-L.; Chen, R.-M. Resveratrol attenuates high-fat diet-induced disruption of the blood–brain barrier and protects brain neurons from apoptotic insults. Journal of agricultural and food chemistry, 2014, 62(15), 3466-3475.

Chelsky, Z.L.; Yue, P.; Kondratyuk, T.P.; Paladino, D.; Pezzuto, J.M.; Cushman, M.; Turkson, J. A Resveratrol Analogue Promotes ERKMAPK–Dependent Stat3 Serine and Tyrosine Phosphorylation Alterations and Antitumor Effects In Vitro against Human Tumor Cells. Molecular pharmacology, 2015, 88(3), 524-533.

Choi, S.; Singh, S.V. Bax and Bak are required for apoptosis induction by sulforaphane, a cruciferous vegetable–derived cancer chemopreventive agent. Cancer research, 2005, 65(5), 2035-2043.

Chun, Y.J.; Kim, M.Y.; Guengerich, F.P. Resveratrol is a selective human cytochrome P450 1A1 inhibitor. Biochemical and biophysical research communications, 1999, 262(1), 20-24.

Clark, P.A.; Bhattacharya, S.; Elmayan, A.; Darjatmoko, S.R.; Thuro, B.A.; Yan, M.B.; van Ginkel, P.R.; Polans, A.S.; Kuo, J.S. Resveratrol targeting of AKT and p53 in glioblastoma and glioblastoma stem-like cells to suppress growth and infiltration. Journal of neurosurgery, 2016, 126(5), 1448-1460.

Conte, A.; Pellegrini, S.; Tagliazucchi, D. Effect of resveratrol and catechin on PC12 tyrosine kinase activities and their synergistic protection from beta-amyloid toxicity. Drugs under experimental and clinical research, 2003, 29(5-6), 243-255.

Couldwell, W.T.; Uhm, J.H.; Antel, J.P.; Yong, V.W. Enhanced protein kinase C activity correlates with the growth rate of malignant gliomas in vitro. Neurosurgery, 1991, 29(6), 880-887.

Coussens, L.M.; Werb, Z. Inflammation and cancer. Nature, 2002, 420(6917), 860.

Cuervo, A.M. Autophagy: in sickness and in health. Trends in cell biology, 2004, 14(2), 70-77.

Dai, Z.; Li, Y.; Quarles, L.; Song, T.; Pan, W.; Zhou, H.; Xiao, Z. Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. Phytomedicine, 2007, 14(12), 806-814.

Dang, C.V. c-Myc target genes involved in cell growth, apoptosis, and metabolism. Molecular and cellular biology, 1999, 19(1), 1-11.

Dao, T.T.; Ha, D.T.; Hien, T.T.; Binh, B.T.; Phuong, T.T.; Long, P.T.; Thu, N.B.; Que, D.T.N.; Khoi, N.M.; Dung, L.V. Resveratrol suppressed lps-induced cox-2 VIA miR-146a-5p inhibition in raw246. 7 cells. Farmacia, 2017, 65(2), 214-218.

Degenhardt, K.; Mathew, R.; Beaudoin, B.; Bray, K.; Anderson, D.; Chen, G.; Mukherjee, C.; Shi, Y.; Gélinas, C.; Fan, Y. Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer cell, 2006, 10(1), 51-64.

Desagher, S.; Glowinski, J.; Premont, J. Astrocytes protect neurons from hydrogen peroxide toxicity. Journal of Neuroscience, 1996, 16(8), 2553-2562.

Dobrzynska, M. Resveratrol as promising natural radioprotector. A review. Roczniki Państwowego Zakładu Higieny, 2013, 64(4).

dos Santos, A.Q.; Nardin, P.; Funchal, C.; de Almeida, L.M.V.; Jacques-Silva, M.C.; Wofchuk, S.T.; Gonçalves, C.-A.; Gottfried, C. Resveratrol increases glutamate uptake and glutamine synthetase activity in C6 glioma cells. Archives of Biochemistry and Biophysics, 2006, 453(2), 161-167.

Dringen, R. Glutathione metabolism and oxidative stress in neurodegeneration. The FEBS Journal, 2000, 267(16), 4903-4903.

Dringen, R.; Gutterer, J.M.; Hirrlinger, J. Glutathione metabolism in brain. The FEBS Journal, 2000, 267(16), 4912-4916.

Dudley, J.; Das, S.; Mukherjee, S.; Das, D.K. RETRACTED: Resveratrol, a unique phytoalexin present in red wine, delivers either survival signal or death signal to the ischemic myocardium depending on dose. In; Elsevier; 2009.

Dutta, D.; Xu, J.; Dirain, M.L.; Leeuwenburgh, C. Calorie restriction combined with resveratrol induces autophagy and protects 26-month-old rat hearts from doxorubicin-induced toxicity. Free Radical Biology and Medicine, 2014, 74, 252-262.

Fimognari, C.; Hrelia, P. Sulforaphane as a promising molecule for fighting cancer. Mutation Research/Reviews in Mutation Research, 2007, 635(2), 90-104.

Firouzi, F.; Khoei, S.; Mirzaei, H.R. Role of resveratrol on the cytotoxic effects and DNA damages of iododeoxyuridine and megavoltage radiation in spheroid culture of U87MG glioblastoma cell line. Gen Physiol Biophys, 2015, 34, 43-50.

Folgueras, A.R.; Pendas, A.M.; Sanchez, L.M.; Lopez-Otin, C. Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. International Journal of Developmental Biology, 2004, 48(5-6), 411-424.

Forsyth, P.; Wong, H.; Laing, T.; Rewcastle, N.; Morris, D.; Muzik, H.; Leco, K.; Johnston, R.; Brasher, P.; Sutherland, G. Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. British journal of cancer, 1999, 79(11-12), 1828.

Fremont, L. Biological effects of resveratrol. Life sciences, 2000, 66(8), 663-673.

Friedlander, M.; Brooks, P.C.; Shaffer, R.W.; Kincaid, C.M.; Varner, J.A.; Cheresh, D.A. Definition of two angiogenic pathways by distinct αv integrins. Science, 1995, 270(5241), 1500-1502.

Gagliano, N.; Aldini, G.; Colombo, G.; Rossi, R.; Colombo, R.; Gioia, M.; Milzani, A.; Dalle-Donne, I. The potential of resveratrol against human gliomas. Anti-cancer drugs, 2010, 21(2), 140-150.

Gagliano, N.; Moscheni, C.; Torri, C.; Magnani, I.; Bertelli, A.A.; Gioia, M. Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and Secreted Protein Acidic and Rich in Cysteine (SPARC) on human cultured glioblastoma cells. Biomedicine & pharmacotherapy, 2005, 59(7), 359-364.

Gagliano, N.; Moscheni, C.; Torri, C.; Magnani, I.; Nowicky, W.; Gioia, M. Matrix metalloproteinase 2 (MMP-2) and secreted protein acidic and rich in cysteine (SPARC) expression in human glioblastoma cells treated with Ukrain: Forum of European Neuroscience, 2006; null.

Gao, X.; Xu, Y.X.; Divine, G.; Janakiraman, N.; Chapman, R.A.; Gautam, S.C. Disparate in vitro and in vivo antileukemic effects of resveratrol, a natural polyphenolic compound found in grapes. The Journal of nutrition, 2002, 132(7), 2076-2081.

Gilbert, M.R.; Friedman, H.S.; Kuttesch, J.F.; Prados, M.D.; Olson, J.J.; Reaman, G.H.; Zaknoen, S.L. A phase II study of temozolomide in patients with newly diagnosed supratentorial malignant glioma before radiation therapy. Neuro-oncology, 2002, 4(4), 261-267.

Guillet, B.; Velly, L.; Canolle, B.; Masmejean, F.; Nieoullon, A.; Pisano, P. Differential regulation by protein kinases of activity and cell surface expression of glutamate transporters in neuron-enriched cultures. Neurochem Int, 2005, 46(4), 337-346.

Hawkins, B.T.; Davis, T.P. The blood-brain barrier/neurovascular unit in health and disease. Pharmacological reviews, 2005, 57(2), 173-185.

Huang, C.; Ma, W.-y.; Goranson, A.; Dong, Z. Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway. Carcinogenesis, 1999, 20(2), 237-242.

Huang, H.; Lin, H.; Zhang, X.; Li, J. Resveratrol reverses temozolomide resistance by downregulation of MGMT in T98G glioblastoma cells by the NF-κB-dependent pathway. Oncology reports, 2012, 27(6), 2050-2056.

Huber, J.D.; Egleton, R.D.; Davis, T.P. Molecular physiology and pathophysiology of tight junctions in the blood–brain barrier. Trends in neurosciences, 2001, 24(12), 719-725.

Jang, M.; Cai, L.; Udeani, G.O.; Slowing, K.V.; Thomas, C.F.; Beecher, C.W.; Fong, H.H.; Farnsworth, N.R.; Kinghorn, A.D.; Mehta, R.G. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 1997, 275(5297), 218-220.

Jiang, H.; Movsesyan, V.; Fink Jr, D.W.; Fasler, M.; Whalin, M.; Katagiri, Y.; Monshipouri, M.; Dickens, G.; Lelkes, P.I.; Guroff, G. Expression of human p140trk receptors in p140trk‐deficient, PC12/endothelial cells results in nerve growth factor‐induced signal transduction and DNA synthesis. Journal of cellular biochemistry, 1997, 66(2), 229-244.

Jiang, H.; Shang, X.; Wu, H.; Huang, G.; Wang, Y.; Al-Holou, S.; Gautam, S.C.; Chopp, M. Combination treatment with resveratrol and sulforaphane induces apoptosis in human U251 glioma cells. Neurochemical research, 2010, 35(1), 152.

Jiang, H.; Zhang, L.; Kuo, J.; Kuo, K.; Gautam, S.C.; Groc, L.; Rodriguez, A.I.; Koubi, D.; Hunter, T.J.; Corcoran, G.B. Resveratrol-induced apoptotic death in human U251 glioma cells. Molecular cancer therapeutics, 2005, 4(4), 554-561.

Jin, Y.H.; Yoo, K.J.; Lee, Y.H.; Lee, S.K. Caspase 3-mediated cleavage of p21 WAF1/CIP1 associated with the cyclin A-cyclin-dependent kinase 2 complex is a prerequisite for apoptosis in SK-HEP-1 cells. Journal of Biological Chemistry, 2000, 275(39), 30256-30263.

Joe, A.K.; Liu, H.; Suzui, M.; Vural, M.E.; Xiao, D.; Weinstein, I.B. Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clinical Cancer Research, 2002, 8(3), 893-903.

Jung, C.H.; Ro, S.-H.; Cao, J.; Otto, N.M.; Kim, D.-H. mTOR regulation of autophagy. FEBS letters, 2010, 584(7), 1287-1295.

Junhong Li, C.L., Seidu A. Richard, Yanhui Liu. Giant solitary primary intracranial lymphoma masquerading as meningioma: a case and review of literature. Pan African Medical Journal, 2017, 28(196).

Kabeya, Y.; Mizushima, N.; Ueno, T.; Yamamoto, A.; Kirisako, T.; Noda, T.; Kominami, E.; Ohsumi, Y.; Yoshimori, T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. The EMBO journal, 2000, 19(21), 5720-5728.

Karmakar, S.; Banik, N.L.; Patel, S.J.; Ray, S.K. Curcumin activated both receptor-mediated and mitochondria-mediated proteolytic pathways for apoptosis in human glioblastoma T98G cells. Neuroscience letters, 2006, 407(1), 53-58.

Khoei, S.; Shoja, M.; Mostaar, A.; Faeghi, F. Effects of resveratrol and methoxyamine on the radiosensitivity of iododeoxyuridine in U87MG glioblastoma cell line. Experimental Biology and Medicine, 2016, 241(11), 1229-1236.

Kim, Y.; Lim, S.-Y.; Rhee, S.-H.; Park, K.Y.; Kim, C.-H.; Choi, B.T.; Lee, S.J.; Park, Y.-M.; Choi, Y.H. Resveratrol inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in β-amyloid-treated C6 glioma cells. International journal of molecular medicine, 2006, 17(6), 1069-1075.

Kimura, Y.; Okuda, H. Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice. The Journal of nutrition, 2001, 131(6), 1844-1849.

Kimura, Y.; Okuda, H.; Kubo, M. Effects of stilbenes isolated from medicinal plants on arachidonate metabolism and degranulation in human polymorphonuclear leukocytes. Journal of ethnopharmacology, 1995, 45(2), 131-139.

Kotha, A.; Sekharam, M.; Cilenti, L.; Siddiquee, K.; Khaled, A.; Zervos, A.S.; Carter, B.; Turkson, J.; Jove, R. Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein. Molecular cancer therapeutics, 2006, 5(3), 621-629.

Kuo, P.-L.; Chiang, L.-C.; Lin, C.-C. Resveratrol-induced apoptosis is mediated by p53-dependent pathway in Hep G2 cells. Life sciences, 2002, 72(1), 23-34.

Leone, S.; Fiore, M.; Lauro, M.G.; Pino, S.; Cornetta, T.; Cozzi, R. Resveratrol and X rays affect gap junction intercellular communications in human glioblastoma cells. Molecular carcinogenesis, 2008, 47(8), 587-598.

Levkau, B.; Koyama, H.; Raines, E.W.; Clurman, B.E.; Herren, B.; Orth, K.; Roberts, J.M.; Ross, R. Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: role of a caspase cascade. Molecular cell, 1998, 1(4), 553-563.

Li, J.; Qin, Z.; Liang, Z. The prosurvival role of autophagy in Resveratrol-induced cytotoxicity in human U251 glioma cells. BMC Cancer, 2009, 9(1), 215.

Lin, H.; Wang, Y.; Zhang, X.; Liu, B.; Zhang, W.; Cheng, J. Prognostic significance of kappaB-Ras1 expression in gliomas. Medical Oncology, 2012, 29(2), 1272-1279.

Lin, H.; Xiong, W.; Zhang, X.; Liu, B.; Zhang, W.; Zhang, Y.; Cheng, J.; Huang, H. Notch-1 activation-dependent p53 restoration contributes to resveratrol-induced apoptosis in glioblastoma cells. Oncology reports, 2011, 26(4), 925-930.

Lin, H.-Y.; Shih, A.; Davis, F.B.; Tang, H.-Y.; Martino, L.J.; Bennett, J.A.; Davis, P.J. Resveratrol induced serine phosphorylation of p53 causes apoptosis in a mutant p53 prostate cancer cell line. The Journal of urology, 2002, 168(2), 748-755.

Lin, H.-Y.; Tang, H.-Y.; Keating, T.; Wu, Y.-H.; Shih, A.; Hammond, D.; Sun, M.; Hercbergs, A.; Davis, F.B.; Davis, P.J. Resveratrol is pro-apoptotic and thyroid hormone is anti-apoptotic in glioma cells: both actions are integrin and ERK mediated. Carcinogenesis, 2007, 29(1), 62-69.

Lomonaco, S.L.; Finniss, S.; Xiang, C.; DeCarvalho, A.; Umansky, F.; Kalkanis, S.N.; Mikkelsen, T.; Brodie, C. The induction of autophagy by γ‐radiation contributes to the radioresistance of glioma stem cells. International journal of cancer, 2009, 125(3), 717-722.

Ma, C.; Wang, Y.; Dong, L.; Li, M.; Cai, W. Anti-inflammatory effect of resveratrol through the suppression of NF-κB and JAK/STAT signaling pathways. Acta biochimica et biophysica Sinica, 2015, 47(3), 207-213.

Maeda, T.; Hobbs, R.M.; Merghoub, T.; Guernah, I.; Zelent, A.; Cordon-Cardo, C.; Teruya-Feldstein, J.; Pandolfi, P.P. Role of the proto-oncogene Pokemon in cellular transformation and ARF repression. Nature, 2005, 433(7023), 278.

Mahyar‐Roemer, M.; Katsen, A.; Mestres, P.; Roemer, K. Resveratrol induces colon tumor cell apoptosis independently of p53 and precede by epithelial differentiation, mitochondrial proliferation and membrane potential collapse. International journal of cancer, 2001, 94(5), 615-622.

Manna, S.K.; Mukhopadhyay, A.; Aggarwal, B.B. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. The Journal of Immunology, 2000, 164(12), 6509-6519.

Manton, K.G.; Volovik, S.; Kulminski, A. ROS effects on neurodegeneration in Alzheimer's disease and related disorders: on environmental stresses of ionizing radiation. Current Alzheimer Research, 2004, 1(4), 277-293.

Marshall, C. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell, 1995, 80(2), 179-185.

Matsuura, E.; Hughes, G.R.; Khamashta, M.A. Oxidation of LDL and its clinical implication. Autoimmunity reviews, 2008, 7(7), 558-566.

Miklossy, G.; Hilliard, T.S.; Turkson, J. Therapeutic modulators of STAT signalling for human diseases. Nature reviews Drug discovery, 2013, 12(8), 611.

Morelli, R.; Das, S.; Bertelli, A.; Bollini, R.; Scalzo, R.L.; Das, D.; Falchi, M. The introduction of the stilbene synthase gene enhances the natural antiradical activity of Lycopersicon esculentum mill. Molecular and cellular biochemistry, 2006, 282(1-2), 65-73.

Morris, G.Z.; Williams, R.L.; Elliott, M.S.; Beebe, S.J. Resveratrol induces apoptosis in LNCaP cells and requires hydroxyl groups to decrease viability in LNCaP and DU 145 cells. The Prostate, 2002, 52(4), 319-329.

Morrison, D.J.; Pendergrast, P.S.; Stavropoulos, P.; Colmenares, S.U.; Kobayashi, R.; Hernandez, N. FBI-1, a factor that binds to the HIV-1 inducer of short transcripts (IST), is a POZ domain protein. Nucleic acids research, 1999, 27(5), 1251-1262.

Mukherjee, S.; Dudley, J.I.; Das, D.K. Dose-dependency of resveratrol in providing health benefits. Dose-Response, 2010, 8(4), dose-response. 09-015. Mukherjee.

Nakada, M.; Okada, Y.; Yamashita, J. The role of matrix metalloproteinases in glioma invasion. Frontiers in bioscience: a journal and virtual library, 2003, 8, e261-269.

Ng, D.C.H.; Lin, B.H.; Lim, C.P.; Huang, G.; Zhang, T.; Poli, V.; Cao, X. Stat3 regulates microtubules by antagonizing the depolymerization activity of stathmin. J Cell Biol, 2006, 172(2), 245-257.

Niles, R.M.; Cook, C.P.; Meadows, G.G.; Fu, Y.-M.; McLaughlin, J.L.; Rankin, G.O. Resveratrol is rapidly metabolized in athymic (nu/nu) mice and does not inhibit human melanoma xenograft tumor growth. The Journal of nutrition, 2006, 136(10), 2542-2546.

Ono, K.; Han, J. The p38 signal transduction pathway activation and function. Cellular signalling, 2000, 12(1), 1-13.

Ovesna, Z.; Horvathova-Kozics, K. Structure-activity relationship of trans-resveratrol and its analogues. Neoplasma, 2005, 52(6), 450.

Pan, G.; Thomson, J.A. Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell research, 2007, 17(1), 42.

Park, D.S.; Morris, E.J.; Greene, L.A.; Geller, H.M. G1/S cell cycle blockers and inhibitors of cyclin-dependent kinases suppress camptothecin-induced neuronal apoptosis. Journal of Neuroscience, 1997, 17(4), 1256-1270.

Park, J.-W.; Choi, Y.-J.; Suh, S.-I.; Baek, W.-K.; Suh, M.-H.; Jin, I.-N.; Min, D.S.; Woo, J.-H.; Chang, J.-S.; Passaniti, A. Bcl-2 overexpression attenuates resveratrol-induced apoptosis in U937 cells by inhibition of caspase-3 activity. Carcinogenesis, 2001, 22(10), 1633-1639.

Pervaiz, S. Resveratrol: from grapevines to mammalian biology. The FASEB Journal, 2003, 17(14), 1975-1985.

Plate, K.H.; Breier, G.; Weich, H.A.; Risau, W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature, 1992, 359(6398), 845.

Rao, J.S. Molecular mechanisms of glioma invasiveness: the role of proteases. Nature Reviews Cancer, 2003, 3(7), 489.

Rego, A.C.; Oliveira, C.R. Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the pathogenesis of neurodegenerative diseases. Neurochemical research, 2003, 28(10), 1563-1574.

Rich, J.N.; Hans, C.; Jones, B.; Iversen, E.S.; McLendon, R.E.; Rasheed, B.A.; Dobra, A.; Dressman, H.K.; Bigner, D.D.; Nevins, J.R. Gene expression profiling and genetic markers in glioblastoma survival. Cancer research, 2005, 65(10), 4051-4058.

Richard S.A, X.L.-H., Yun J.-X., Shanshan Z, Jiang Y.-Y, Wang J,; Su Z.-L, X.H.-X. Carcinogenic and therapeutic role of High-Mobility Group Box 1 in Cancer: is it a cancer facilitator, a cancer inhibitor or both? World Cancer Research Journal, 2017, 4(3), e919.

Richard, S.A.; Jiang, Y.; Xiang, L.H.; Zhou, S.; Wang, J.; Su, Z.; Xu, H. Post-translational modifications of high mobility group box 1 and cancer. Am J Transl Res, 2017, 9(12), 5181-5196.

Richard, S.A.; Liang, R.F.; Lei, C.F.; Liu, Y.H. Diffuse leptomeningeal tuberculoma masquerading as leptomeningeal gliomatosis: a case report and review of literature. Infectious Diseases & Tropical Medicine, 2017, 3(3), e406.

Richard, S.A.; Ma, L.; Li, H.; Li, J.; You, C. Giant intradural cervical spine arteriovenous malformations–A case and review of literature. Neurologia i neurochirurgia polska, 2018.

Richard, S.A.; Min, W.; Su, Z.; Xu, H. High Mobility Group Box 1 and Traumatic Brain Injury. Journal of Behavioral and Brain Science, 2017, 7(02), 50.

Richard, S.A.; Min, W.; Su, Z.; Xu, H.-X. Epochal neuroinflammatory role of high mobility group box 1 in central nervous system diseases. AIMS Molecular Science, 2017, 4(2), 185-218.

Richard, S.A.; Sackey, M.; Su, Z.; Xu, H. Pivotal neuroinflammatory and therapeutic role of high mobility group box 1 in ischemic stroke. Bioscience reports, 2017.

Richard, S.A.; Tampouri, J.; Sackey, M.; Zakariah, A.N. Human immunodeficiency virus and cerebrovascular diseases–review. HIV & AIDS Review, 2017, 16(4).

Richard, S.A.; Zheng, S.; Su, Z.; Gao, J.; Xu, H. The Pivotal Neuroinflammatory, Therapeutic and Neuroprotective Role of Alpha-Mangostin. Journal of Neurology Research, 2017, 7(4-5), 67-79.

Risau, W. Mechanisms of angiogenesis. Nature, 1997, 386(6626), 671.

Ryu, J.; Ku, B.M.; Lee, Y.K.; JEONG, J.Y.; Kang, S.; Choi, J.; Yang, Y.; Lee, D.H.; Roh, G.S.; Kim, H.J. Resveratrol reduces TNF-α-induced U373MG human glioma cell invasion through regulating NF-κB activation and uPA/uPAR expression. Anticancer research, 2011, 31(12), 4223-4230.

Sato, A.; Okada, M.; Shibuya, K.; Watanabe, E.; Seino, S.; Suzuki, K.; Narita, Y.; Shibui, S.; Kayama, T.; Kitanaka, C. Resveratrol promotes proteasome-dependent degradation of Nanog via p53 activation and induces differentiation of glioma stem cells. Stem cell research, 2013, 11(1), 601-610.

Sato, H.; Kita, M.; Seiki, M. v-Src activates the expression of 92-kDa type IV collagenase gene through the AP-1 site and the GT box homologous to retinoblastoma control elements. A mechanism regulating gene expression independent of that by inflammatory cytokines. Journal of Biological Chemistry, 1993, 268(31), 23460-23468.

Sato, H.; Seiki, M. Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene, 1993, 8(2), 395-405.

Sato, H.; Takino, T.; Okada, Y.; Cao, J.; Shinagawa, A.; Yamamoto, E.; Seiki, M. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature, 1994, 370(6484), 61.

Schultz, C.; Lemke, N.; Ge, S.; Golembieski, W.A.; Rempel, S.A. Secreted protein acidic and rich in cysteine promotes glioma invasion and delays tumor growth in vivo. Cancer research, 2002, 62(21), 6270-6277.

Schulz, C.A.; Mehta, M.P.; Badie, B.; McGinn, C.J.; Robins, H.I.; Hayes, L.; Chappell, R.; Volkman, J.; Binger, K.; Arzoomanian, R. Continuous 28-day iododeoxyuridine infusion and hyperfractionated accelerated radiotherapy for malignant glioma: a phase I clinical study. International Journal of Radiation Oncology• Biology• Physics, 2004, 59(4), 1107-1115.

Schütz, A.; Röser, K.; Klitzsch, J.; Lieder, F.; Aberger, F.; Gruber, W.; Mueller, K.M.; Pupyshev, A.; Moriggl, R.; Friedrich, K. Lung adenocarcinomas and lung cancer cell lines show association of MMP-1 expression with STAT3 activation. Translational oncology, 2015, 8(2), 97-105.

Seidu, R.A.; Wu, M.; Su, Z.; Xu, H. Paradoxical role of high mobility group box 1 in glioma: a suppressor or a promoter? Oncology Reviews, 2017, 11(1).

Sharma, G.M. Hypoxia inducible factor-1α (HIF-1 α) and its role in tumour progression to malignancy. Online Journal of Health and Allied Sciences, 2008, 7(2).

She, Q.-B.; Bode, A.M.; Ma, W.-Y.; Chen, N.-Y.; Dong, Z. Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase. Cancer research, 2001, 61(4), 1604-1610.

Shi, Q.; Bao, S.; Maxwell, J.A.; Reese, E.D.; Friedman, H.S.; Bigner, D.D.; Wang, X.-F.; Rich, J.N. Secreted protein acidic, rich in cysteine (SPARC), mediates cellular survival of gliomas through AKT activation. Journal of Biological Chemistry, 2004, 279(50), 52200-52209.

Shi, Q.; Bao, S.; Song, L.; Wu, Q.; Bigner, D.; Hjelmeland, A.; Rich, J. Targeting SPARC expression decreases glioma cellular survival and invasion associated with reduced activities of FAK and ILK kinases. Oncogene, 2007, 26(28), 4084.

Shindler, K.S.; Ventura, E.; Dutt, M.; Elliott, P.; Fitzgerald, D.C.; Rostami, A. Oral resveratrol reduces neuronal damage in a model of multiple sclerosis. Journal of Neuro-Ophthalmology, 2010, 30(4), 328.

Shishodia, S.; Koul, D.; Aggarwal, B.B. Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates TNF-induced NF-κB activation through inhibition of activation of IκBα kinase and Akt in human non-small cell lung carcinoma: correlation with suppression of COX-2 synthesis. The Journal of Immunology, 2004, 173(3), 2011-2022.

Singh, N.P.; Hegde, V.L.; Hofseth, L.J.; Nagarkatti, M.; Nagarkatti, P. Resveratrol (trans-3, 5, 4′-trihydroxystilbene) ameliorates experimental allergic encephalomyelitis, primarily via induction of apoptosis in T cells involving activation of aryl hydrocarbon receptor and estrogen receptor. Molecular pharmacology, 2007, 72(6), 1508-1521.

Soleas, G.J.; Diamandis, E.P.; Goldberg, D.M. Resveratrol: a molecule whose time has come? And gone? Clinical biochemistry, 1997, 30(2), 91-113.

Soroceanu, L.; Manning, T.J.; Sontheimer, H. Reduced expression of connexin‐43 and functional gap junction coupling in human gliomas. Glia, 2001, 33(2), 107-117.

Stojic, J.; Hagemann, C.; Haas, S.; Herbold, C.; Kühnel, S.; Gerngras, S.; Roggendorf, W.; Roosen, K.; Vince, G.H. Expression of matrix metalloproteinases MMP-1, MMP-11 and MMP-19 is correlated with the WHO-grading of human malignant gliomas. Neuroscience research, 2008, 60(1), 40-49.

Su, Z.; Ni, P.; She, P.; Liu, Y.; Richard, S.A.; Xu, W.; Zhu, H.; Wang, J. Bio-HMGB1 from breast cancer contributes to M-MDSC differentiation from bone marrow progenitor cells and facilitates conversion of monocytes into MDSC-like cells. Cancer Immunology, Immunotherapy, 2017, 66(3), 391-401.

Subbaramaiah, K.; Chung, W.J.; Michaluart, P.; Telang, N.; Tanabe, T.; Inoue, H.; Jang, M.; Pezzuto, J.M.; Dannenberg, A.J. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. Journal of Biological Chemistry, 1998, 273(34), 21875-21882.

Sun, C.-y.; Hu, Y.; Guo, T.; Wang, H.-f.; Zhang, X.-p.; He, W.-j.; Tan, H. Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity. Acta pharmacologica Sinica, 2006, 27(11), 1447.

Takuma, K.; Baba, A.; Matsuda, T. Astrocyte apoptosis: implications for neuroprotection. Progress in neurobiology, 2004, 72(2), 111-127.

Tang, H.-Y.; Shih, A.; Cao, H.J.; Davis, F.B.; Davis, P.J.; Lin, H.-Y. Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells. Molecular cancer therapeutics, 2006, 5(8), 2034-2042.

Trung, L.Q.; Espinoza, J.L.; Takami, A.; Nakao, S. Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition. PLoS One, 2013, 8(1), e55183.

Tseng, S.-H.; Lin, S.-M.; Chen, J.-C.; Su, Y.-H.; Huang, H.-Y.; Chen, C.-K.; Lin, P.-Y.; Chen, Y. Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats. Clinical Cancer Research, 2004, 10(6), 2190-2202.

Tsujimoto, M.; Yip, Y.; Vilcek, J. Tumor necrosis factor: specific binding and internalization in sensitive and resistant cells. Proceedings of the National Academy of Sciences, 1985, 82(22), 7626-7630.

Udenigwe, C.C.; Ramprasath, V.R.; Aluko, R.E.; Jones, P.J. Potential of resveratrol in anticancer and anti-inflammatory therapy. Nutrition reviews, 2008, 66(8), 445-454.

Van Ginkel, P.R.; Sareen, D.; Subramanian, L.; Walker, Q.; Darjatmoko, S.R.; Lindstrom, M.J.; Kulkarni, A.; Albert, D.M.; Polans, A.S. Resveratrol inhibits tumor growth of human neuroblastoma and mediates apoptosis by directly targeting mitochondria. Clinical Cancer Research, 2007, 13(17), 5162-5169.

Vidavalur, R.; Otani, H.; Singal, P.K.; Maulik, N. Significance of wine and resveratrol in cardiovascular disease: French paradox revisited. Experimental & Clinical Cardiology, 2006, 11(3), 217.

Vihinen, P.; Ala-aho, R.; Kahari, V.-M. Matrix metalloproteinases as therapeutic targets in cancer. Current cancer drug targets, 2005, 5(3), 203-220.

Vitaglione, P.; Sforza, S.; Galaverna, G.; Ghidini, C.; Caporaso, N.; Vescovi, P.P.; Fogliano, V.; Marchelli, R. Bioavailability of trans‐resveratrol from red wine in humans. Molecular nutrition & food research, 2005, 49(5), 495-504.

Von Marschall, Z.; Cramer, T.; Höcker, M.; Burde, R.; Plath, T.; Schirner, M.; Heidenreich, R.; Breier, G.; Riecken, E.O.; Wiedenmann, B. De novo expression of vascular endothelial growth factor in human pancreatic cancer: evidence for an autocrine mitogenic loop. Gastroenterology, 2000, 119(5), 1358-1372.

Wallach, D.; Varfolomeev, E.; Malinin, N.; Goltsev, Y.V.; Kovalenko, A.; Boldin, M. Tumor necrosis factor receptor and Fas signaling mechanisms. Annual review of immunology, 1999, 17(1), 331-367.

Walle, T.; Hsieh, F.; DeLegge, M.H.; Oatis, J.E.; Walle, U.K. High absorption but very low bioavailability of oral resveratrol in humans. Drug metabolism and disposition, 2004, 32(12), 1377-1382.

Wang, D.; Li, S.-P.; Fu, J.-S.; Zhang, S.; Bai, L.; Guo, L. Resveratrol defends blood-brain barrier integrity in experimental autoimmune encephalomyelitis mice. Journal of neurophysiology, 2016, 116(5), 2173-2179.

Wang, G.; Dai, F.; Yu, K.; Jia, Z.; Zhang, A.; Huang, Q.; Kang, C.; Jiang, H.; Pu, P. Resveratrol inhibits glioma cell growth via targeting oncogenic microRNAs and multiple signaling pathways. International journal of oncology, 2015, 46(4), 1739-1747.

Wang, H.; Feng, H.; Zhang, Y. Resveratrol inhibits hypoxia-induced glioma cell migration and invasion by the p-STAT3/miR-34a axis. Neoplasma, 2016, 63(4), 532-539.

Wang, L.; Long, L.; Wang, W.; Liang, Z. Resveratrol, a potential radiation sensitizer for glioma stem cells both in vitro and in vivo. Journal of pharmacological sciences, 2015, 129(4), 216-225.

Wang, M.; Huang, H.; Hsieh, S.; Jeng, K.; Kuo, J. Resveratrol inhibits interleukin-6 production in cortical mixed glial cells under hypoxia/hypoglycemia followed by reoxygenation. Journal of neuroimmunology, 2001, 112(1), 28-34.

Wang, M.; Wang, T.; Liu, S.; Yoshida, D.; Teramoto, A. The expression of matrix metalloproteinase-2 and-9 in human gliomas of different pathological grades. Brain tumor pathology, 2003, 20(2), 65-72.

Wang, Q.; Xu, J.; Rottinghaus, G.E.; Simonyi, A.; Lubahn, D.; Sun, G.Y.; Sun, A.Y. Resveratrol protects against global cerebral ischemic injury in gerbils. Brain research, 2002, 958(2), 439-447.

Weidner, N.; Folkman, J.; Pozza, F.; Bevilacqua, P.; Allred, E.N.; Moore, D.H.; Meli, S.; Gasparini, G. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. JNCI: Journal of the National Cancer Institute, 1992, 84(24), 1875-1887.

Weisburger, J.H. Carcinogenicity and mutagenicity testing, then and now. Mutation Research/Reviews in Mutation Research, 1999, 437(2), 105-112.

Wenzel, E.; Somoza, V. Metabolism and bioavailability of trans‐resveratrol. Molecular nutrition & food research, 2005, 49(5), 472-481.

Williams, J.R.; Zhang, Y.; Zhou, H.; Gridley, D.S.; Koch, C.J.; Slater, J.M.; Little, J.B. Overview of radiosensitivity of human tumor cells to low-dose-rate irradiation. International Journal of Radiation Oncology• Biology• Physics, 2008, 72(3), 909-917.

Wolburg, H.; Lippoldt, A. Tight junctions of the blood–brain barrier: development, composition and regulation. Vascular pharmacology, 2002, 38(6), 323-337.

Wolter, F.; Akoglu, B.; Clausnitzer, A.; Stein, J. Downregulation of the cyclin D1/Cdk4 complex occurs during resveratrol-induced cell cycle arrest in colon cancer cell lines. The Journal of nutrition, 2001, 131(8), 2197-2203.

Woo, J.-H.; Lim, J.H.; Kim, Y.-H.; Suh, S.-I.; Chang, J.-S.; Lee, Y.H.; Park, J.-W.; Kwon, T.K. Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC δ signal transduction. Oncogene, 2004, 23(10), 1845.

Xu, W.; Lu, Y.; Yao, J.; Li, Z.; Chen, Z.; Wang, G.; Jing, H.; Zhang, X.; Li, M.; Peng, J. Novel role of resveratrol: suppression of high-mobility group protein box 1 nucleocytoplasmic translocation by the upregulation of sirtuin 1 in sepsis-induced liver injury. Shock, 2014, 42(5), 440-447.

Yang, C.S.; Landau, J.M.; Huang, M.-T.; Newmark, H.L. Inhibition of carcinogenesis by dietary polyphenolic compounds. Annual review of nutrition, 2001, 21(1), 381-406.

Yang, Y.; Cui, J.; Xue, F.; Overstreet, A.-M.; Zhan, Y.; Shan, D.; Li, H.; Wang, Y.; Zhang, M.; Yu, C. Resveratrol represses pokemon expression in human glioma cells. Molecular neurobiology, 2016, 53(2), 1266-1278.

Yu, H.; Jove, R. The STATs of cancer—new molecular targets come of age. Nature Reviews Cancer, 2004, 4(2), 97.

Yu, L.; Alva, A.; Su, H.; Dutt, P.; Freundt, E.; Welsh, S.; Baehrecke, E.H.; Lenardo, M.J. Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science, 2004, 304(5676), 1500-1502.

Yu, L.-J.; Wu, M.-L.; Li, H.; Chen, X.-Y.; Wang, Q.; Sun, Y.; Kong, Q.-Y.; Liu, J. Inhibition of STAT3 expression and signaling in resveratrol-differentiated medulloblastoma cells. Neoplasia, 2008, 10(7), 736-744.

Zainal, N.; Chang, C.-P.; Cheng, Y.-L.; Wu, Y.-W.; Anderson, R.; Wan, S.-W.; Chen, C.-L.; Ho, T.-S.; AbuBakar, S.; Lin, Y.-S. Resveratrol treatment reveals a novel role for HMGB1 in regulation of the type 1 interferon response in dengue virus infection. Scientific reports, 2017, 7, 42998.

Zhang, Q.; Tang, X.; Lu, Q.Y.; Zhang, Z.F.; Brown, J.; Le, A.D. Resveratrol inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1α and VEGF expression in human tongue squamous cell carcinoma and hepatoma cells. Molecular cancer therapeutics, 2005, 4(10), 1465-1474.

Zhuang, W.; Li, B.; Long, L.; Chen, L.; Huang, Q.; Liang, Z. Induction of autophagy promotes differentiation of glioma‐initiating cells and their radiosensitivity. International journal of cancer, 2011, 129(11), 2720-2731.

Zucker, S.; Lysik, R.M.; Zarrabi, M.H.; Moll, U. Mr 92,000 type IV collagenase is increased in plasma of patients with colon cancer and breast cancer. Cancer research, 1993, 53(1), 140-146.



  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

2013-2022 (CC-BY) Australian International Academic Centre PTY.LTD.

Advances in Bioscience and Clinical Medicine