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Natural products as promising targets in glioblastoma multiforme: a focus on NF-κB signaling pathway

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Abstract

Background

Glioblastoma multiforme (GBM), as the broadest cerebrum tumor, is resistant to current medical interventions, particularly chemo/radiation. Hence, it necessitates further therapeutic options that could enhance the efficacy of existing modalities.

Methods

A comprehensive and systematic review of literature on the NF-κB signaling pathway-contributed in the pathogenesis of GBM with a focus on natural products was carried out.

Results

Several examinations have shown that nuclear factor (NF)-κB is participated in apoptosis, cellular proliferation, angiogenesis, metastasis, invasion, and many other processes implicated in GBM pathobiology. Recent studies have provided that NF-κB regulation is the primary pharmacological target for GBM therapy. Specific natural products are involved in several signaling pathways implicated in tumor growth and apoptosis of GBM cells.

Conclusion

In the current review, we elaborate on the role of NF-κB as a promising target in GBM and discuss some natural products affecting the NF-κB signaling pathway.

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References

  1. Xiao H, Bai J, Yan M, Ji K, Tian W, Liu D, et al. Metastatic glioblastoma multiforme: a rare case of long-term survival. Biomed Res. 2018;29:1120–2.

    Google Scholar 

  2. Afshari AR, Karimi Roshan M, Soukhtanloo M, Ghorbani A, Rahmani F, Jalili-Nik M, et al. Cytotoxic effects of auraptene against a human malignant glioblastoma cell line. Avicenna J Phytomed. 2019;9:334–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Afshari AR, Jalili-Nik M, Soukhtanloo M, Ghorbani A, Sadeghnia HR, Mollazadeh H, et al. Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells: role of reactive oxygen species (ROS). EXCLI J. 2019;18:576–90.

    PubMed  PubMed Central  Google Scholar 

  4. Jalili-Nik M, Sabri H, Zamiri E, Soukhtanloo M, Roshan MK, Hosseini A, et al. Cytotoxic effects of ferula latisecta on human glioma U87 cells. Drug Res (Stuttg). 2019;69:665–70.

    CAS  PubMed  Google Scholar 

  5. Guan X, Hasan MN, Maniar S, Jia W, Sun D. Reactive astrocytes in glioblastoma multiforme. Mol Neurobiol. 2018;55:6927–38.

    CAS  PubMed  Google Scholar 

  6. Hintenlang LL, Miller DH, Kaleem T, Patel N, May BC, Tzou KS, et al. Treatment of a glioblastoma multiforme dural metastasis with stereotactic radiosurgery: a case report and select review of the literature. J Clin Neurosci. 2018;48:118–21.

    PubMed  Google Scholar 

  7. Gray GK, McFarland BC, Nozell SE, Benveniste EN. NF-kappaB and STAT3 in glioblastoma: therapeutic targets coming of age. Expert Rev Neurother. 2014;14:1293–306.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Murray PG, Flavell JR, Baumforth KR, Toomey SM, Lowe D, Crocker J, et al. Expression of the tumour necrosis factor receptor-associated factors 1 and 2 in Hodgkin’s disease. J Pathol. 2001;194:158–64.

    CAS  PubMed  Google Scholar 

  9. Messaoudi K, Clavreul A, Lagarce F. Toward an effective strategy in glioblastoma treatment. Part I: resistance mechanisms and strategies to overcome resistance of glioblastoma to temozolomide. Drug Discov Today. 2015;20:899–905.

    CAS  PubMed  Google Scholar 

  10. Taniguchi K, Karin M. NF-kappaB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018;18:309–24.

    CAS  PubMed  Google Scholar 

  11. Puliyappadamba VT, Hatanpaa KJ, Chakraborty S, Habib AA. The role of NF-kappaB in the pathogenesis of glioma. Mol Cell Oncol. 2014;1:e963478.

    PubMed  PubMed Central  Google Scholar 

  12. Sun SC. Non-canonical NF-kappaB signaling pathway. Cell Res. 2011;21:71–85.

    CAS  PubMed  Google Scholar 

  13. Park MH, Hong JT. Roles of NF-kappaB in cancer and inflammatory diseases and their therapeutic approaches. Cells. 2016;5:15.

    PubMed Central  Google Scholar 

  14. Zhou Y, Eppenberger-Castori S, Eppenberger U, Benz CC. The NFkappaB pathway and endocrine-resistant breast cancer. Endocr Relat Cancer. 2005;12(Suppl 1):S37–46.

    CAS  PubMed  Google Scholar 

  15. Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006;25:6680–4.

    CAS  PubMed  Google Scholar 

  16. Dolcet X, Llobet D, Pallares J, Matias-Guiu X. NF-kB in development and progression of human cancer. Virchows Arch. 2005;446:475–82.

    CAS  PubMed  Google Scholar 

  17. Grivennikov SI, Karin M. Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev. 2010;21:11–9.

    CAS  PubMed  Google Scholar 

  18. Richmond A, Yang J. The role of NF-kB in modulating antitumor immunity. Oncoimmunology. 2016;5:e1005522.

    PubMed  Google Scholar 

  19. Yamini B, Yu X, Dolan ME, Wu MH, Darga TE, Kufe DW, et al. Inhibition of nuclear factor-kappaB activity by temozolomide involves O6-methylguanine induced inhibition of p65 DNA binding. Cancer Res. 2007;67:6889–98.

    CAS  PubMed  Google Scholar 

  20. Nagai S, Washiyama K, Kurimoto M, Takaku A, Endo S, Kumanishi T. Aberrant nuclear factor-kappaB activity and its participation in the growth of human malignant astrocytoma. J Neurosurg. 2002;96:909–17.

    CAS  PubMed  Google Scholar 

  21. Galvani E, Sun J, Leon LG, Sciarrillo R, Narayan RS, Sjin RT, et al. NF-kappaB drives acquired resistance to a novel mutant-selective EGFR inhibitor. Oncotarget. 2015;6:42717–32.

    PubMed  PubMed Central  Google Scholar 

  22. Takada Y, Kobayashi Y, Aggarwal BB. Evodiamine abolishes constitutive and inducible NF-kappaB activation by inhibiting IkappaBalpha kinase activation, thereby suppressing NF-kappaB-regulated antiapoptotic and metastatic gene expression, up-regulating apoptosis, and inhibiting invasion. J Biol Chem. 2005;280:17203–12.

    CAS  PubMed  Google Scholar 

  23. Xia Y, Shen S, Verma IM. NF-kappaB, an active player in human cancers. Cancer Immunol Res. 2014;2:823–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Atkinson GP, Nozell SE, Benveniste ET. NF-kappaB and STAT3 signaling in glioma: targets for future therapies. Expert Rev Neurother. 2010;10:575–86.

    CAS  PubMed  Google Scholar 

  25. Song L, Liu L, Wu Z, Li Y, Ying Z, Lin C, et al. TGF-beta induces miR-182 to sustain NF-kappaB activation in glioma subsets. J Clin Investig. 2012;122:3563–78.

    CAS  PubMed  Google Scholar 

  26. Karimi Roshan M, Soltani A, Soleimani A, Rezaie Kahkhaie K, Afshari AR, Soukhtanloo M. Role of AKT and mTOR signaling pathways in the induction of epithelial-mesenchymal transition (EMT) process. Biochimie. 2019;165:229–34.

    CAS  PubMed  Google Scholar 

  27. Salminen A, Lehtonen M, Suuronen T, Kaarniranta K, Huuskonen J. Terpenoids: natural inhibitors of NF-kappaB signaling with anti-inflammatory and anticancer potential. Cell Mol Life Sci. 2008;65:2979–99.

    CAS  PubMed  Google Scholar 

  28. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, et al. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol. 2004;5:503–7.

    CAS  PubMed  Google Scholar 

  29. Festjens N, Vanden Berghe T, Cornelis S, Vandenabeele P. RIP1, a kinase on the crossroads of a cell’s decision to live or die. Cell Death Differ. 2007;14:400–10.

    CAS  PubMed  Google Scholar 

  30. Bonavia R, Inda MM, Vandenberg S, Cheng SY, Nagane M, Hadwiger P, et al. EGFRvIII promotes glioma angiogenesis and growth through the NF-kappaB, interleukin-8 pathway. Oncogene. 2012;31:4054–66.

    CAS  PubMed  Google Scholar 

  31. Xie T-X, Xia Z, Zhang N, Gong W, Huang S. Constitutive NF-κB activity regulates the expression of VEGF and IL-8 and tumor angiogenesis of human glioblastoma. Oncol Rep. 2010;23:725–32.

    CAS  PubMed  Google Scholar 

  32. Shostak K, Chariot A. EGFR and NF-kappaB: partners in cancer. Trends Mol Med. 2015;21:385–93.

    CAS  PubMed  Google Scholar 

  33. Dan HC, Cooper MJ, Cogswell PC, Duncan JA, Ting JP, Baldwin AS. Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK. Genes Dev. 2008;22:1490–500.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Bai D, Ueno L, Vogt PK. Akt-mediated regulation of NFkappaB and the essentialness of NFkappaB for the oncogenicity of PI3K and Akt. Int J Cancer. 2009;125:2863–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Kapoor GS, Zhan Y, Johnson GR, O’Rourke DM. Distinct domains in the SHP-2 phosphatase differentially regulate epidermal growth factor receptor/NF-kappaB activation through Gab1 in glioblastoma cells. Mol Cell Biol. 2004;24:823–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Pearson JRD, Regad T. Targeting cellular pathways in glioblastoma multiforme. Signal Transduct Target Ther. 2017;2:17040.

    PubMed  PubMed Central  Google Scholar 

  37. Puliyappadamba VT, Chakraborty S, Chauncey SS, Li L, Hatanpaa KJ, Mickey B, et al. Opposing effect of EGFRWT on EGFRvIII-mediated NF-kappaB activation with RIP1 as a cell death switch. Cell Rep. 2013;4:764–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Robe PA, Bentires-Alj M, Bonif M, Rogister B, Deprez M, Haddada H, et al. In vitro and in vivo activity of the nuclear factor-kappaB inhibitor sulfasalazine in human glioblastomas. Clin Cancer Res. 2004;10:5595–603.

    CAS  PubMed  Google Scholar 

  39. Wieland A, Trageser D, Gogolok S, Reinartz R, Hofer H, Keller M, et al. Anticancer effects of niclosamide in human glioblastoma. Clin Cancer Res. 2013;19:4124–36.

    CAS  PubMed  Google Scholar 

  40. Zanotto-Filho A, Braganhol E, Battastini AM, Moreira JC. Proteasome inhibitor MG132 induces selective apoptosis in glioblastoma cells through inhibition of PI3K/Akt and NFkappaB pathways, mitochondrial dysfunction, and activation of p38-JNK1/2 signaling. Investig New Drugs. 2012;30:2252–62.

    CAS  Google Scholar 

  41. Zanotto-Filho A, Braganhol E, Schroder R, de Souza LH, Dalmolin RJ, Pasquali MA, et al. NFkappaB inhibitors induce cell death in glioblastomas. Biochem Pharmacol. 2011;81:412–24.

    CAS  PubMed  Google Scholar 

  42. Dutta S, Mahalanobish S, Saha S, Ghosh S, Sil PC. Natural products: An upcoming therapeutic approach to cancer. Food Chem Toxicol. 2019;128:240–55.

    CAS  PubMed  Google Scholar 

  43. Pejin B, Simonovic M, Talevska A, Glumac M, Jakimov D, Kojic V. A neglected natural source for targeting glioblastoma. Nat Prod Res. 2019. https://doi.org/10.1080/14786419.2019.1638386.

    Article  PubMed  Google Scholar 

  44. Pejin B, Tommonaro G, Glumac M, Jakimov D, Kojic V. The redox couple avarol/avarone in the fight with malignant gliomas: the case study of U-251 MG cells. Nat Prod Res. 2018;32:616–20.

    CAS  PubMed  Google Scholar 

  45. Pejin B, Glumac M. A brief review of potent anti-CNS tumourics from marine sponges: covering the period from 1994 to 2014. Nat Prod Res. 2018;32:375–84.

    CAS  PubMed  Google Scholar 

  46. Pejin B, Jovanovic KK, Mojovic M, Savic AG. New and highly potent antitumor natural products from marine-derived fungi: covering the period from 2003 to 2012. Curr Top Med Chem. 2013;13:2745–66.

    CAS  PubMed  Google Scholar 

  47. Weaver BA. How Taxol/paclitaxel kills cancer cells. Mol Biol Cell. 2014;25:2677–81.

    PubMed  PubMed Central  Google Scholar 

  48. Gascoigne KE, Taylor SS. How do anti-mitotic drugs kill cancer cells? J Cell Sci. 2009;122:2579–85.

    CAS  PubMed  Google Scholar 

  49. Parajuli P, Joshee N, Chinni SR, Rimando AM, Mittal S, Sethi S, et al. Delayed growth of glioma by Scutellaria flavonoids involve inhibition of Akt, GSK-3 and NF-kappaB signaling. J Neurooncol. 2011;101:15–24.

    PubMed  Google Scholar 

  50. Tommonaro G, Pejin B, Iodice C, Tafuto A, De Rosa S. Further in vitro biological activity evaluation of amino-, thio- and ester-derivatives of avarol. J Enzyme Inhib Med Chem. 2015;30:333–5.

    CAS  PubMed  Google Scholar 

  51. Pejin B, Iodice C, Tommonaro G, De Rosa S. Synthesis and biological activities of thio-avarol derivatives. J Nat Prod. 2008;71:1850–3.

    CAS  PubMed  Google Scholar 

  52. Tommonaro G, Garcia-Font N, Vitale RM, Pejin B, Iodice C, Canadas S, et al. Avarol derivatives as competitive AChE inhibitors, non hepatotoxic and neuroprotective agents for Alzheimer’s disease. Eur J Med Chem. 2016;122:326–38.

    CAS  PubMed  Google Scholar 

  53. Pejin B, Iodice C, Tommonaro G, Stanimirovic B, Ciric A, Glamoclija J, et al. Further in vitro evaluation of antimicrobial activity of the marine sesquiterpene hydroquinone avarol. Curr Pharm Biotechnol. 2014;15:583–8.

    CAS  PubMed  Google Scholar 

  54. Pejin B, Iodice C, Kojic V, Jakimov D, Lazovic M, Tommonaro G. In vitro evaluation of cytotoxic and mutagenic activity of avarol. Nat Prod Res. 2016;30:1293–6.

    CAS  PubMed  Google Scholar 

  55. Ren Z, Wang L, Cui J, Huoc Z, Xue J, Cui H, et al. Resveratrol inhibits NF-κB signaling through suppression of p65 and IB kinase activities. Pharmazie. 2013;68:689–94.

    CAS  PubMed  Google Scholar 

  56. Cheemanapalli S, Chinthakunta N, Shaikh NM, Shivaranjani V, Pamuru RR, Chitta SK. Comparative binding studies of curcumin and tangeretin on up-stream elements of NF-kB cascade: a combined molecular docking approach. Netw Model Anal Health Inform Bioinform. 2019;8:15.

    Google Scholar 

  57. Khan H, Ullah H, Castilho P, Gomila AS, D’Onofrio G, Filosa R, et al. Targeting NF-kappaB signaling pathway in cancer by dietary polyphenols. Crit Rev Food Sci Nutr. 2019. https://doi.org/10.1080/10408398.2019.1661827.

    Article  PubMed  Google Scholar 

  58. Kumar D, Dwivedi DK, Lahkar M, Jangra A. Hepatoprotective potential of 7,8-dihydroxyflavone against alcohol and high-fat diet induced liver toxicity via attenuation of oxido-nitrosative stress and NF-kappaB activation. Pharmacol Rep. 2019;71:1235–43.

    CAS  PubMed  Google Scholar 

  59. Luqman S, Pezzuto JM. NFkappaB: a promising target for natural products in cancer chemoprevention. Phytother Res. 2010;24:949–63.

    CAS  PubMed  Google Scholar 

  60. El-Readi MZ, Eid S, Abdelghany AA, Al-Amoudi HS, Efferth T, Wink M. Resveratrol mediated cancer cell apoptosis, and modulation of multidrug resistance proteins and metabolic enzymes. Phytomedicine. 2019;55:269–81.

    CAS  PubMed  Google Scholar 

  61. Vervandier-Fasseur D, Latruffe N. The potential use of resveratrol for cancer prevention. Molecules. 2019;24:4506.

    CAS  PubMed Central  Google Scholar 

  62. Jiao Y, Li H, Liu Y, Guo A, Xu X, Qu X, et al. Resveratrol inhibits the invasion of glioblastoma-initiating cells via down-regulation of the PI3K/Akt/NF-kappaB signaling pathway. Nutrients. 2015;7:4383–402.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Westhoff MA, Zhou S, Nonnenmacher L, Karpel-Massler G, Jennewein C, Schneider M, et al. Inhibition of NF-kappaB signaling ablates the invasive phenotype of glioblastoma. Mol Cancer Res. 2013;11:1611–23.

    CAS  PubMed  Google Scholar 

  64. Huang H, Lin H, Zhang X, Li J. Resveratrol reverses temozolomide resistance by downregulation of MGMT in T98G glioblastoma cells by the NF-kappaB-dependent pathway. Oncol Rep. 2012;27:2050–6.

    CAS  PubMed  Google Scholar 

  65. Li F, Sethi G. Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. Biochim Biophys Acta. 2010;1805:167–80.

    CAS  PubMed  Google Scholar 

  66. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.

    CAS  PubMed  Google Scholar 

  67. Arepalli SK, Choi M, Jung JK, Lee H. Novel NF-kappaB inhibitors: a patent review (2011–2014). Expert Opin Ther Pat. 2015;25:319–34.

    CAS  PubMed  Google Scholar 

  68. Reyes-Farias M, Carrasco-Pozo C. The anti-cancer effect of quercetin: molecular implications in cancer metabolism. Int J Mol Sci. 2019;20:3177.

    CAS  PubMed Central  Google Scholar 

  69. Liu Y, Tang ZG, Lin Y, Qu XG, Lv W, Wang GB, et al. Effects of quercetin on proliferation and migration of human glioblastoma U251 cells. Biomed Pharmacother. 2017;92:33–8.

    PubMed  Google Scholar 

  70. Kiekow CJ, Figueiro F, Dietrich F, Vechia LD, Pires EN, Jandrey EH, et al. Quercetin derivative induces cell death in glioma cells by modulating NF-kappaB nuclear translocation and caspase-3 activation. Eur J Pharm Sci. 2016;84:116–22.

    CAS  PubMed  Google Scholar 

  71. Park MH, Ahn BH, Hong YK, Min do S. Overexpression of phospholipase D enhances matrix metalloproteinase-2 expression and glioma cell invasion via protein kinase C and protein kinase A/NF-kappaB/Sp1-mediated signaling pathways. Carcinogenesis. 2009;30:356–65.

    CAS  PubMed  Google Scholar 

  72. Tang W, Liang R, Duan Y, Shi Q, Liu X, Liao Y. PLD1 overexpression promotes invasion and migration and function as a risk factor for Chinese glioma patients. Oncotarget. 2017;8:57039–46.

    PubMed  PubMed Central  Google Scholar 

  73. Park MH, Min do S. Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells. Biochem Biophys Res Commun. 2011;412:710–5.

    CAS  PubMed  Google Scholar 

  74. Yan X, Qi M, Li P, Zhan Y, Shao H. Apigenin in cancer therapy: anti-cancer effects and mechanisms of action. Cell Biosci. 2017;7:50.

    PubMed  PubMed Central  Google Scholar 

  75. Erdogan S, Doganlar O, Doganlar ZB, Serttas R, Turkekul K, Dibirdik I, et al. The flavonoid apigenin reduces prostate cancer CD44(+) stem cell survival and migration through PI3K/Akt/NF-kappaB signaling. Life Sci. 2016;162:77–86.

    CAS  PubMed  Google Scholar 

  76. Qin Y, Zhao D, Zhou HG, Wang XH, Zhong WL, Chen S, et al. Apigenin inhibits NF-kappaB and snail signaling, EMT and metastasis in human hepatocellular carcinoma. Oncotarget. 2016;7:41421–31.

    PubMed  PubMed Central  Google Scholar 

  77. Chang X, He H, Zhu L, Gao J, Wei T, Ma Z, et al. Protective effect of apigenin on Freund’s complete adjuvant-induced arthritis in rats via inhibiting P2X7/NF-kappaB pathway. Chem Biol Interact. 2015;236:41–6.

    CAS  PubMed  Google Scholar 

  78. Chen XJ, Wu MY, Li DH, You J. Apigenin inhibits glioma cell growth through promoting microRNA-16 and suppression of BCL-2 and nuclear factor-kappaB/MMP9. Mol Med Rep. 2016;14:2352–8.

    CAS  PubMed  Google Scholar 

  79. Brunelli D, Tavecchio M, Falcioni C, Frapolli R, Erba E, Iori R, et al. The isothiocyanate produced from glucomoringin inhibits NF-kB and reduces myeloma growth in nude mice in vivo. Biochem Pharmacol. 2010;79:1141–8.

    CAS  PubMed  Google Scholar 

  80. Prawan A, Saw CL, Khor TO, Keum YS, Yu S, Hu L, et al. Anti-NF-kappaB and anti-inflammatory activities of synthetic isothiocyanates: effect of chemical structures and cellular signaling. Chem Biol Interact. 2009;179:202–11.

    CAS  PubMed  Google Scholar 

  81. Subedi L, Venkatesan R, Kim SY. Neuroprotective and anti-inflammatory activities of allyl isothiocyanate through attenuation of JNK/NF-kappaB/TNF-alpha signaling. Int J Mol Sci. 2017;18:1423.

    PubMed Central  Google Scholar 

  82. Guo Z, Wang H, Wei J, Han L, Li Z. Sequential treatment of phenethyl isothiocyanate increases sensitivity of Temozolomide resistant glioblastoma cells by decreasing expression of MGMT via NF-κB pathway. Am J Transl Res. 2019;11:696.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Lee CS, Cho HJ, Jeong YJ, Shin JM, Park KK, Park YY, et al. Isothiocyanates inhibit the invasion and migration of C6 glioma cells by blocking FAK/JNK-mediated MMP-9 expression. Oncol Rep. 2015;34:2901–8.

    CAS  PubMed  Google Scholar 

  84. Cheung KL, Kong A-N. Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. AAPS J. 2010;12:87–97.

    CAS  PubMed  Google Scholar 

  85. Clarke JD, Dashwood RH, Ho E. Multi-targeted prevention of cancer by sulforaphane. Cancer Lett. 2008;269:291–304.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Xu C, Shen G, Chen C, Gelinas C, Kong AN. Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells. Oncogene. 2005;24:4486–95.

    CAS  PubMed  Google Scholar 

  87. Lenzi M, Fimognari C, Hrelia P. Sulforaphane as a promising molecule for fighting cancer. Cancer Treat Res. 2014;159:207–23.

    CAS  PubMed  Google Scholar 

  88. Huang TY, Chang WC, Wang MY, Yang YR, Hsu YC. Effect of sulforaphane on growth inhibition in human brain malignant glioma GBM 8401 cells by means of mitochondrial- and MEK/ERK-mediated apoptosis pathway. Cell Biochem Biophys. 2012;63:247–59.

    CAS  PubMed  Google Scholar 

  89. Chun J, Choi RJ, Khan S, Lee DS, Kim YC, Nam YJ, et al. Alantolactone suppresses inducible nitric oxide synthase and cyclooxygenase-2 expression by down-regulating NF-kappaB, MAPK and AP-1 via the MyD88 signaling pathway in LPS-activated RAW 264.7 cells. Int Immunopharmacol. 2012;14:375–83.

    CAS  PubMed  Google Scholar 

  90. Wei W, Huang H, Zhao S, Liu W, Liu CX, Chen L, et al. Alantolactone induces apoptosis in chronic myelogenous leukemia sensitive or resistant to imatinib through NF-kappaB inhibition and Bcr/Abl protein deletion. Apoptosis. 2013;18:1060–70.

    CAS  PubMed  Google Scholar 

  91. Rasul A, Khan M, Ali M, Li J, Li X. Targeting apoptosis pathways in cancer with alantolactone and isoalantolactone. Sci World J. 2013;2013:248532.

    Google Scholar 

  92. Khan M, Yi F, Rasul A, Li T, Wang N, Gao H, et al. Alantolactone induces apoptosis in glioblastoma cells via GSH depletion, ROS generation, and mitochondrial dysfunction. IUBMB Life. 2012;64:783–94.

    CAS  PubMed  Google Scholar 

  93. Wang X, Yu Z, Wang C, Cheng W, Tian X, Huo X, et al. Alantolactone, a natural sesquiterpene lactone, has potent antitumor activity against glioblastoma by targeting IKKbeta kinase activity and interrupting NF-kappaB/COX-2-mediated signaling cascades. J Exp Clin Cancer Res. 2017;36:93.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Seo MB, Lee SK, Jeon YJ, Im JS. Inhibition of p65 nuclear translocation by baicalein. Toxicol Res. 2011;27:71–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Yu X, Liu Y, Wang Y, Mao X, Zhang Y, Xia J. Baicalein induces cervical cancer apoptosis through the NF-kappaB signaling pathway. Mol Med Rep. 2018;17:5088–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Jiang G, Zhang L, Wang J, Zhou H. Baicalein induces the apoptosis of U251 glioblastoma cell lines via the NF-kB-p65-mediated mechanism. Anim Cells Syst. 2016;20:296–302.

    CAS  Google Scholar 

  97. Kwok BHB, Koh B, Ndubuisi MI, Elofsson M, Crews CM. The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IκB kinase. Chem Biol. 2001;8:759–66.

    CAS  PubMed  Google Scholar 

  98. Heptinstall S. Feverfew—an ancient remedy for modern times? J R Soc Med. 1988;81:373.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Haffner MC, Berlato C, Doppler W. Exploiting our knowledge of NF-kappaB signaling for the treatment of mammary cancer. J Mammary Gland Biol Neoplasia. 2006;11:63–73.

    PubMed  Google Scholar 

  100. Yu Z, Chen Y, Wang S, Li P, Zhou G, Yuan Y. Inhibition of NF-kappaB results in anti-glioma activity and reduces temozolomide-induced chemoresistance by down-regulating MGMT gene expression. Cancer Lett. 2018;428:77–89.

    CAS  PubMed  Google Scholar 

  101. Nakabayashi H, Shimizu K. Involvement of Akt/NF-kappaB pathway in antitumor effects of parthenolide on glioblastoma cells in vitro and in vivo. BMC Cancer. 2012;12:453.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Anderson KN, Bejcek BE. Parthenolide induces apoptosis in glioblastomas without affecting NF-kappaB. J Pharmacol Sci. 2008;106:318–20.

    CAS  PubMed  Google Scholar 

  103. Wang CN, Shiao YJ, Lin YL, Chen CF. Nepalolide A inhibits the expression of inducible nitric oxide synthase by modulating the degradation of IkappaB-alpha and IkappaB-beta in C6 glioma cells and rat primary astrocytes. Br J Pharmacol. 1999;128:345–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Saberi-Karimian M, Katsiki N, Caraglia M, Boccellino M, Majeed M, Sahebkar A. Vascular endothelial growth factor: an important molecular target of curcumin. Crit Rev Food Sci Nutr. 2019;59:299–312.

    CAS  PubMed  Google Scholar 

  105. Cheng A-L, Hsu C-H, Lin J-K, Hsu M-M, Ho Y-F, Shen T-S, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21:2895–900.

    CAS  PubMed  Google Scholar 

  106. Ambegaokar SS, Wu L, Alamshahi K, Lau J, Jazayeri L, Chan S, et al. Curcumin inhibits dose-dependently and time-dependently neuroglial cell proliferation and growth. Neuro Endocrinol Lett. 2003;24:469.

    CAS  PubMed  Google Scholar 

  107. Gao X, Deeb D, Jiang H, Liu YB, Dulchavsky SA, Gautam SC. Curcumin differentially sensitizes malignant glioma cells to TRAIL/Apo2L-mediated apoptosis through activation of procaspases and release of cytochrome c from mitochondria. J Exp Ther Oncol. 2005;5:39–48.

    PubMed  Google Scholar 

  108. Kim SY, Jung SH, Kim HS. Curcumin is a potent broad spectrum inhibitor of matrix metalloproteinase gene expression in human astroglioma cells. Biochem Biophys Res Commun. 2005;337:510–6.

    CAS  PubMed  Google Scholar 

  109. Dhandapani KM, Mahesh VB, Brann DW. Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors. J Neurochem. 2007;102:522–38.

    CAS  PubMed  Google Scholar 

  110. Zhao J, Zhu J, Lv X, Xing J, Liu S, Chen C, et al. Curcumin potentiates the potent antitumor activity of ACNU against glioblastoma by suppressing the PI3K/AKT and NF-kappaB/COX-2 signaling pathways. Onco Targets Ther. 2017;10:5471–82.

    PubMed  PubMed Central  Google Scholar 

  111. Fratantonio D, Molonia MS, Bashllari R, Muscara C, Ferlazzo G, Costa G, et al. Curcumin potentiates the antitumor activity of Paclitaxel in rat glioma C6 cells. Phytomedicine. 2019;55:23–30.

    PubMed  Google Scholar 

  112. Kumar R, Lal N, Nemaysh V, Luthra PM. Demethoxycurcumin mediated targeting of MnSOD leading to activation of apoptotic pathway and inhibition of Akt/NF-kappaB survival signalling in human glioma U87 MG cells. Toxicol Appl Pharmacol. 2018;345:75–93.

    CAS  PubMed  Google Scholar 

  113. Karmakar S, Weinberg MS, Banik NL, Patel SJ, Ray SK. Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane. Neuroscience. 2006;141:1265–80.

    CAS  PubMed  Google Scholar 

  114. Mollazadeh H, Afshari AR, Hosseinzadeh H. Review on the potential therapeutic roles of nigella sativa in the treatment of patients with cancer: involvement of apoptosis:-black cumin and cancer. J Pharmacopunct. 2017;20:158–72.

    Google Scholar 

  115. Gerstner ER, Fine RL. Increased permeability of the blood-brain barrier to chemotherapy in metastatic brain tumors: establishing a treatment paradigm. J Clin Oncol. 2007;25:2306–12.

    PubMed  Google Scholar 

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Acknowledgements

The authors would like to honor Dr. Sima Khosravi, a kind physician and a great mother to the corresponding author (A. R. A), who lost her battle with GBM disease in the fall of 2016.

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  1. Mohammad Soukhtanloo and Elmira Mohtashami equally contributed to this work.

Authors and Affiliations

  1. Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Soukhtanloo, Mostafa Karimi Roshan & Mohammad Jalili-Nik

  2. Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

    Elmira Mohtashami & Azar Hosseini

  3. Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Abolfazl Maghrouni

  4. Department of Physiology and Pharmacology, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

    Hamid Mollazadeh & Amir R. Afshari

  5. Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Hadi Mousavi

  6. Social Development and Health Promotion Research Center, Gonabad University of Medical Sciences, Gonabad, Iran

    Seyed-Amir Tabatabaeizadeh

  7. Department of Pharmacology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

    Mohammad Mahdi Vahedi

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  1. Mohammad Soukhtanloo
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Correspondence to Amir R. Afshari.

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Soukhtanloo, M., Mohtashami, E., Maghrouni, A. et al. Natural products as promising targets in glioblastoma multiforme: a focus on NF-κB signaling pathway. Pharmacol. Rep 72, 285–295 (2020). https://doi.org/10.1007/s43440-020-00081-7

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  • DOI: https://doi.org/10.1007/s43440-020-00081-7

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