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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Focus on the Use of Resveratrol as an Adjuvant in Glioblastoma Therapy

Author(s): Lamberto Dionigi, Francesco Ragonese, Lorenzo Monarca, Stefano Covino, Antonella de Luca, Rossana G. Iannitti, Federica Bastioli, Anargyros N. Moulas, Marcello Allegretti* and Bernard Fioretti*

Volume 26, Issue 18, 2020

Page: [2102 - 2108] Pages: 7

DOI: 10.2174/1381612826666200401085634

Price: $65

Abstract

Glioblastoma (GB) represents the most common and malignant form of glioma cancer. The Gold Standard in Glioblastoma is neurosurgical tumor removal and radiotherapy treatment in concomitant with temozolomide (TMZ). Unfortunately, because of tumor chemo and radio-resistance during this therapy, the patient’s outcome remains very poor, with a median overall survival of about 14.6 months. Resveratrol is a natural polyphenol with a stilbene structure with chemopreventive and anticancer properties. In the present review, we evaluated data from preclinical studies conducted with resveratrol as a possible adjuvant during the standard protocol of GB. Resveratrol can reach the brain parenchyma at sub-micromolar concentrations when administrated through conventional routes. In this way, resveratrol reduces cell invasion and increases the efficacy of radiotherapy (radiosensitizer effects) and temozolomide. The molecular mechanism of the adjuvant action of resveratrol may depend upon the reduction of PI3K/AKT/NF-κB axis and downstream targets O-6-methylguanine-DNA methyltransferase (MGMT) and metalloproteinase-2 (MMP-2). It has been reported that redox signaling plays an important role in the regulation of autophagy. Resveratrol administration by External Carotid Artery (ECA) injection or by Lumbar Puncture (LP) can reach micromolar concentrations in tumor mass where it would inhibit tumor growth by STAT-3 dependent mechanisms. Preclinical evidences indicate a positive effect on the use of resveratrol as an adjuvant in anti-GB therapy. Ameliorated formulations of resveratrol with a favorable plasmatic profile for a better brain distribution and timing sequences during radio and chemotherapy could represent a critical aspect for resveratrol use as an adjuvant for a clinical evaluation.

Keywords: Glioblastoma, Resveratrol, adjuvant of anticancer therapy, preclinical study, anti-invasion, radiosensitizer.

« Previous Next »
[1]
Holland EC. Gliomagenesis: genetic alterations and mouse models. Nat Rev Genet 2001; 2(2): 120-9.
[http://dx.doi.org/10.1038/35052535] [PMID: 11253051]
[2]
Holash J, Maisonpierre PC, Compton D, et al. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 1999; 284(5422): 1994-8.
[http://dx.doi.org/10.1126/science.284.5422.1994] [PMID: 10373119]
[3]
Hardee ME, Zagzag D. Mechanisms of glioma-associated neovascularization. Am J Pathol 2012; 181(4): 1126-41.
[http://dx.doi.org/10.1016/j.ajpath.2012.06.030] [PMID: 22858156]
[4]
Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 2016; 131(6): 803-20.
[http://dx.doi.org/10.1007/s00401-016-1545-1] [PMID: 27157931]
[5]
Ahmed R, Oborski MJ, Hwang M, Lieberman FS, Mountz JM. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods. Cancer Manag Res 2014; 6(6): 149-70.
[PMID: 24711712]
[6]
The Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008; 455(7216): 1061-8.
[http://dx.doi.org/10.1038/nature07385] [PMID: 18772890]
[7]
Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006; 444(7120): 756-60.
[http://dx.doi.org/10.1038/nature05236] [PMID: 17051156]
[8]
Keles GE, Anderson B, Berger MS. The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere. Surg Neurol 1999; 52(4): 371-9.
[http://dx.doi.org/10.1016/S0090-3019(99)00103-2] [PMID: 10555843]
[9]
Lacroix M, Abi-Said D, Fourney DR, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 2001; 95(2): 190-8.
[http://dx.doi.org/10.3171/jns.2001.95.2.0190] [PMID: 11780887]
[10]
Sheline GE. Radiotherapy for high grade gliomas. Int J Radiat Oncol Biol Phys 1990; 18(4): 793-803.
[http://dx.doi.org/10.1016/0360-3016(90)90399-5] [PMID: 2182578]
[11]
Douglas JG, Stelzer KJ, Mankoff DA, et al. [F-18]-fluorodeoxyglucose positron emission tomography for targeting radiation dose escalation for patients with glioblastoma multiforme: clinical outcomes and patterns of failure. Int J Radiat Oncol Biol Phys 2006; 64(3): 886-91.
[http://dx.doi.org/10.1016/j.ijrobp.2005.08.013] [PMID: 16242251]
[12]
Ghose A, Lim G, Husain S. Treatment for glioblastoma multiforme: current guidelines and Canadian practice. Curr Oncol 2010; 17(6): 52-8.
[http://dx.doi.org/10.3747/co.v17i6.574] [PMID: 21151410]
[13]
Begum N, Wang B, Mori M, Vares G. Does ionizing radiation influence Alzheimer’s disease risk? J Radiat Res (Tokyo) 2012; 53(6): 815-22.
[http://dx.doi.org/10.1093/jrr/rrs036] [PMID: 22872779]
[14]
Keime-Guibert F, Chinot O, Taillandier L, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med 2007; 356(15): 1527-35.
[http://dx.doi.org/10.1056/NEJMoa065901] [PMID: 17429084]
[15]
Stupp R, Hegi ME, Neyns B, et al. Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol 2010; 28(16): 2712-8.
[http://dx.doi.org/10.1200/JCO.2009.26.6650] [PMID: 20439646]
[16]
Hottinger AF, Stupp R, Homicsko K. Standards of care and novel approaches in the management of glioblastoma multiforme. Chin J Cancer 2014; 33(1): 32-9.
[http://dx.doi.org/10.5732/cjc.013.10207] [PMID: 24384238]
[17]
Friedman HS, Kerby T, Calvert H. Temozolomide and treatment of malignant glioma. Clin Cancer Res 2000; 6(7): 2585-97.
[PMID: 10914698]
[18]
Robinson K, Mock C, Liang D. Pre-formulation studies of resveratrol. Drug Dev Ind Pharm 2015; 41(9): 1464-9.
[http://dx.doi.org/10.3109/03639045.2014.958753] [PMID: 25224342]
[19]
Shah VP, Amidon GLGL GL Amidon, H. Lennernäs, V.P. Shah JR, Crison . A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12: 413-20.
[http://dx.doi.org/10.1208/s12248-014-9620-9] [PMID: 24961917]
[20]
Xiao Q, Zhu W, Feng W, et al. A Review of resveratrol as a potent chemoprotective and synergistic agent in cancer chemotherapy. Front Pharmacol 2019; 9: 1534.
[http://dx.doi.org/10.3389/fphar.2018.01534] [PMID: 30687096]
[21]
Rauf A, Imran M, Suleria HAR, Ahmad B, Peters DG, Mubarak MS. A comprehensive review of the health perspectives of resveratrol. Food Funct 2017; 8(12): 4284-305.
[http://dx.doi.org/10.1039/C7FO01300K] [PMID: 29044265]
[22]
Tomé-Carneiro J, Larrosa M, González-Sarrías A, Tomás-Barberán FA, García-Conesa MT, Espín JC. Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des 2013; 19(34): 6064-93.
[http://dx.doi.org/10.2174/13816128113199990407] [PMID: 23448440]
[23]
Elshaer M, Chen Y, Wang XJ, Tang X. Resveratrol: An overview of its anti-cancer mechanisms. Life Sci 2018; 207: 340-9.
[http://dx.doi.org/10.1016/j.lfs.2018.06.028] [PMID: 29959028]
[24]
Huang XT, Li X, Xie ML, et al. Resveratrol: Review on its discovery, anti-leukemia effects and pharmacokinetics. Chem Biol Interact 2019; 306: 29-38.
[http://dx.doi.org/10.1016/j.cbi.2019.04.001] [PMID: 30954463]
[25]
Sun Z, Li H, Shu XH, et al. Distinct sulfonation activities in resveratrol-sensitive and resveratrol-insensitive human glioblastoma cells. FEBS J 2012; 279(13): 2381-92.
[http://dx.doi.org/10.1111/j.1742-4658.2012.08617.x] [PMID: 22540632]
[26]
Filippi-Chiela EC, Thomé MP, Bueno e Silva MM, et al. Resveratrol abrogates the temozolomide-induced G2 arrest leading to mitotic catastrophe and reinforces the temozolomide-induced senescence in glioma cells. BMC Cancer 2013; 13: 147-60.
[http://dx.doi.org/10.1186/1471-2407-13-147] [PMID: 23522185]
[27]
Jiang H, Zhang L, Kuo J, et al. Resveratrol-induced apoptotic death in human U251 glioma cells. Mol Cancer Ther 2005; 4(4): 554-61.
[http://dx.doi.org/10.1158/1535-7163.MCT-04-0056] [PMID: 15827328]
[28]
Li J, Qin Z, Liang Z. The prosurvival role of autophagy in Resveratrol-induced cytotoxicity in human U251 glioma cells. BMC Cancer 2009; 9: 215.
[http://dx.doi.org/10.1186/1471-2407-9-215] [PMID: 19566920]
[29]
Shu XH, Li H, Sun XX, et al. Metabolic patterns and biotransformation activities of resveratrol in human glioblastoma cells: relevance with therapeutic efficacies. PLoS One 2011; 6(11): e27484-93.
[http://dx.doi.org/10.1371/journal.pone.0027484] [PMID: 22096581]
[30]
Leone S, Fiore M, Lauro MG, Pino S, Cornetta T, Cozzi R. Resveratrol and X rays affect gap junction intercellular communications in human glioblastoma cells. Mol Carcinog 2008; 47(8): 587-98.
[http://dx.doi.org/10.1002/mc.20416] [PMID: 18286483]
[31]
Yuan Y, Xue X, Guo RB, Sun XL, Hu G. Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway. CNS Neurosci Ther 2012; 18(7): 536-46.
[http://dx.doi.org/10.1111/j.1755-5949.2012.00319.x] [PMID: 22530672]
[32]
Guo W, Li A, Jia Z, Yuan Y, Dai H, Li H. Transferrin modified PEG-PLA-resveratrol conjugates: in vitro and in vivo studies for glioma. Eur J Pharmacol 2013; 718(1-3): 41-7.
[http://dx.doi.org/10.1016/j.ejphar.2013.09.034] [PMID: 24070814]
[33]
Castino R, Pucer A, Veneroni R, et al. Resveratrol reduces the invasive growth and promotes the acquisition of a long-lasting differentiated phenotype in human glioblastoma cells. J Agric Food Chem 2011; 59(8): 4264-72.
[http://dx.doi.org/10.1021/jf104917q] [PMID: 21395220]
[34]
Gagliano N, Moscheni C, Torri C, Magnani I, Bertelli AA, 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. Biomed Pharmacother 2005; 59(7): 359-64.
[http://dx.doi.org/10.1016/j.biopha.2005.06.001] [PMID: 16084059]
[35]
Jiao Y, Li H, Liu Y, et al. Resveratrol inhibits the invasion of glioblastoma-initiating cells via down-regulation of the PI3K/Akt/NF-κB signaling pathway. Nutrients 2015; 7(6): 4383-402.
[http://dx.doi.org/10.3390/nu7064383] [PMID: 26043036]
[36]
Xiong W, Yin A, Mao X, Zhang W, Huang H, Zhang X. Resveratrol suppresses human glioblastoma cell migration and invasion via activation of RhoA/ROCK signaling pathway. Oncol Lett 2016; 11(1): 484-90.
[http://dx.doi.org/10.3892/ol.2015.3888] [PMID: 26870238]
[37]
Tseng SH, Lin SM, Chen JC, et al. Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats. Clin Cancer Res 2004; 10(6): 2190-202.
[http://dx.doi.org/10.1158/1078-0432.CCR-03-0105] [PMID: 15041740]
[38]
Clark PA, Bhattacharya S, Elmayan A, et al. Resveratrol targeting of AKT and p53 in glioblastoma and glioblastoma stem-like cells to suppress growth and infiltration. J Neurosurg 2017; 126(5): 1448-60.
[http://dx.doi.org/10.3171/2016.1.JNS152077] [PMID: 27419830]
[39]
Song Y, Chen Y, Li Y, et al. Resveratrol suppresses epithelial-mesenchymal transition in GBM by regulating smad-dependent signaling. BioMed Res Int 2019; 2019: 1321973
[http://dx.doi.org/10.1155/2019/1321973] [PMID: 31119150]
[40]
Wang L, Long L, Wang W, Liang Z. Resveratrol, a potential radiation sensitizer for glioma stem cells both in vitro and in vivo. J Pharmacol Sci 2015; 129(4): 216-25.
[http://dx.doi.org/10.1016/j.jphs.2015.11.001] [PMID: 26698406]
[41]
Lin CJ, Lee CC, Shih YL, et al. Resveratrol enhances the therapeutic effect of temozolomide against malignant glioma in vitro and in vivo by inhibiting autophagy. Free Radic Biol Med 2012; 52(2): 377-91.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.487] [PMID: 22094224]
[42]
Chen JC, Chen Y, Lin JH, Wu JM, Tseng SH. Resveratrol suppresses angiogenesis in gliomas: evaluation by color Doppler ultrasound. Anticancer Res 2006; 26(2A): 1237-45.
[PMID: 16619530]
[43]
Yang YP, Chang YL, Huang PI, et al. Resveratrol suppresses tumorigenicity and enhances radiosensitivity in primary glioblastoma tumor initiating cells by inhibiting the STAT3 axis. J Cell Physiol 2012; 227(3): 976-93.
[http://dx.doi.org/10.1002/jcp.22806] [PMID: 21503893]
[44]
Shu XH, Wang LL, Li H, et al. Diffusion efficiency and bioavailability of resveratrol administered to rat brain by different routes: therapeutic implications. Neurotherapeutics 2015; 12(2): 491-501.
[http://dx.doi.org/10.1007/s13311-014-0334-6] [PMID: 25588581]
[45]
Xue S, Xiao-Hong S, Lin S, et al. Lumbar puncture-administered resveratrol inhibits STAT3 activation, enhancing autophagy and apoptosis in orthotopic rat glioblastomas. Oncotarget 2016; 7(46): 75790-9.
[http://dx.doi.org/10.18632/oncotarget.12414] [PMID: 27716625]
[46]
Song X, Shu XH, Wu ML, et al. Postoperative resveratrol administration improves prognosis of rat orthotopic glioblastomas. BMC Cancer 2018; 18(1): 871-81.
[http://dx.doi.org/10.1186/s12885-018-4771-1] [PMID: 30176837]
[47]
Asensi M, Medina I, Ortega A, et al. Inhibition of cancer growth by resveratrol is related to its low bioavailability. Free Radic Biol Med 2002; 33(3): 387-98.
[http://dx.doi.org/10.1016/S0891-5849(02)00911-5] [PMID: 12126761]
[48]
Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol 2000; 164(12): 6509-19.
[http://dx.doi.org/10.4049/jimmunol.164.12.6509] [PMID: 10843709]
[49]
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. Oncol Rep 2012; 27(6): 2050-6.
[PMID: 22426504]
[50]
Sontheimer H. Ion channels and amino acid transporters support the growth and invasion of primary brain tumors. Mol Neurobiol 2004; 29(1): 61-71.
[http://dx.doi.org/10.1385/MN:29:1:61] [PMID: 15034223]
[51]
Colin D, Limagne E, Jeanningros S, et al. Endocytosis of resveratrol via lipid rafts and activation of downstream signaling pathways in cancer cells. Cancer Prev Res (Phila) 2011; 4(7): 1095-106.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0274] [PMID: 21467134]
[52]
Amri A, Chaumeil JC, Sfar S, Charrueau C. Administration of resveratrol: What formulation solutions to bioavailability limitations? J Control Release 2012; 158(2): 182-93.
[http://dx.doi.org/10.1016/j.jconrel.2011.09.083] [PMID: 21978644]
[53]
Chimento A, De Amicis F, Sirianni R, et al. Progress to improve oral bioavailability and beneficial effects of resveratrol. Int J Mol Sci 2019; 20(6): 1381-408.
[http://dx.doi.org/10.3390/ijms20061381] [PMID: 30893846]
[54]
Spogli R, Bastianini M, Ragonese F, Iannitti RG, Monarca L, Bastioli F. Solid Dispersion of resveratrol supported on magnesium dihydroxide (Resv@MDH) microparticles improves oral bioavailability. Nutrients 2018; 5: 10(12): pii: E1925.
[55]
Ianitti A, Floridi A, Lazzarini A, et al. Resveratrol supported on magnesium DiHydroxide (Resv@MDH, REVIFAST) represents an improved formulation of resveratrol with fast absorption and bioavailability in humans. J Biotechnol 2019; 305: S17.
[http://dx.doi.org/10.1016/j.jbiotec.2019.05.071]

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