Advertisement

Therapeutic potential of natural products in glioblastoma treatment: targeting key glioblastoma signaling pathways and epigenetic alterations

  • M. N. Abbas
  • S. Kausar
  • H. CuiEmail author
Review Article

Abstract

Glioma is the most common primary tumor of the nervous system, and approximately 50% of patients exhibit the most aggressive form of the cancer, glioblastoma. Currently, considerable research in glioblastoma therapeutics is aimed at developing vaccines or drugs to target key molecules for combating this disease. Studies on plant natural products from spices, vegetables, fruits, teas, and traditional medicinal herbs display that these plant-derived natural products can act as effective antioxidant and anti-tumor agents. The advancements in metabolomics and in genomics have enabled researchers to better evaluate the potential use of immunomodulatory natural plant products for treatment of different cancerous diseases. The glioblastoma protective activities of the different natural plant products lie in their effects on cellular defenses such as antioxidant enzyme systems, detoxification and the stimulation of anti-inflammatory, anti-metastasis responses and by modifying epigenetic alterations, often through targeting specific key transcription factors such as activator protein, nuclear factor kappa B, signal transducers and activators of transcription and so on. Here, we review recent knowledge on the molecular mechanisms by which different inflammatory activities are linked to progression of glioblastoma and the particular immunomodulatory plant products that may reduce inflammation and the associated progression and metastasis of glioblastoma both in vitro and in vivo. Furthermore, their impact on the epigenetic alterations will also be discussed.

Keywords

Glioblastoma Therapeutic targeting Natural compounds Cell proliferation Epigenetic regulators 

Notes

Funding

This study was funded by the National Key Research and Development Program of China (Grant number 2016YFC1302204 and 2017YFC1308600) and by the National Natural Science Foundation of China (Grant number 81672502 to H. Cui).

Compliance with ethical standards

Conflict of interest

MNA declares that he has no conflict of interest. SK declares that she has no conflict of interest. HC declares that she has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

References

  1. 1.
    Lin TY, Lee CC, Chen KC, Lin CJ, Shih CM. Inhibition of RNA transportation induces glioma cell apoptosis via downregulation of RanGAP1 expression. Chem Biol Interact. 2015;232:49–57.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    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;18:536–46.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature. 2004;432:396–401.CrossRefGoogle Scholar
  4. 4.
    Chen R, et al. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell. 2012;148:1293–307.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Kim H, Moon JY, Ahn KS, Cho SK. Quercetin induces mitochondrial mediated apoptosis and protective autophagy in human glioblastoma U373MG cells. Oxid Med Cell Longev. 2013;2013:596496.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Salvesen GS, Duckett CS. IAP proteins: blocking the road to death’s door. Nat Rev Mol Cell Biol. 2002;3:401–10.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Khaw AK, Sameni S, Venkatesan S, Kalthur G, Hande MP. Plumbagin alters telomere dynamics, induces DNA damage and cell death in human brain tumour cells. Mutat Res Genet Toxicol Environ Mutagen. 2015;793:86–95.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Mishra R, Kaur G. Aqueous ethanolic extract of Tinospora cordifolia as a potential candidate for differentiation based therapy of glioblastomas. PLoS One. 2013;8:e78764.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Guerram M, Jiang ZZ, Sun L, Zhu X, Zhang LY. Antineoplastic effects of deoxypodophyllotoxin, a potent cytotoxic agent of plant origin, on glioblastoma U-87 MG and SF126 cells. Pharmacol Rep. 2015;67:245–52.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Hahm SW, Park J, Son YS. Opuntia humifusa partitioned extracts inhibit the growth of U87MG human glioblastoma cells. Plant Foods Hum Nutr. 2010;65:247–52.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Michaud-Levesque J, Bousquet-Gagnon N, Beliveau R. Quercetin abrogates IL-6/STAT3 signaling and inhibits glioblastoma cell line growth and migration. Exp Cell Res. 2012;318:925–35.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Racoma IO, Meisen WH, Wang QE, Kaur B, Wani AA. Thymoquinone inhibits autophagy and induces cathepsin mediated, caspase-independent cell death in glioblastoma cells. PLoS One. 2013;8:e72882.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Abdullah Thani NA, Sallis B, Nuttall R, Schubert FR, Ahsan M, Davies D, Purewal S, Cooper A, Rooprai HK. Induction of apoptosis and reduction of MMP gene expression in the U373 cell line by polyphenolics in Aronia melanocarpa and by curcumin. Oncol Rep. 2012;28:1435–42.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Liu Q, Xu X, Zhao M, Wei Z, Li X, Zhang X, Liu Z, Gong Y, Shao C. Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway. Mol Cancer Ther. 2015;14:355–63.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Suresh D, Srinivasan K. Tissue distribution & elimination of capsaicin, piperine & curcumin following oral intake in rats. Indian J Med Res. 2010;131:682–91.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Ramachandran C, Portalatin G, Quirin KW, Escalon E, Khatib Z, Melnick SJ. Inhibition of AKT signaling by supercritical CO2 extract of mango ginger (Curcuma amada Roxb.) in human glioblastoma cells. J Complement Integr Med. 2015;12:307–15.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Kuete V, Sandjo LP, Ouete JL, Fouotsa H, Wiench B, Efferth T. Cytotoxicity and modes of action of three naturally occurring xanthones (8-hydroxycudraxanthone G, morusignin I and cudraxanthone I) against sensitive and multidrug-resistant cancer cell lines. Phytomedicine. 2014;21:315–22.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Li Y, Zhang P, Qiu F, Chen L, Miao C, Li J, Xiao W, Ma E. Inactivation of PI3K/Akt signaling mediates proliferation inhibition and G2/M phase arrest induced by andrographolide in human glioblastoma cells. Life Sci. 2012;90:962–7.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Bates S, Parry D, Bonetta L, Vousden K, Dickson C, et al. Absence of cyclin D/cdk complexes in cells lacking functional retinoblastoma protein. Oncogene. 1994;9:1633–40.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Aravindaram K, Yang NS. Anti-inflammatory plant natural products for cancer therapy. Planta Med. 2010;76:1103–17.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Perry MC, Demeule M, Regina A, Moumdjian R, Beliveau R. Curcumin inhibits tumor growth and angiogenesis in glioblastoma xenografts. Mol Nutr Food Res. 2010;54:1192–201.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Miao J, Jiang Y, Wang D, Zhou J, Fan C, Jiao F, Liu B, Zhang J, Wang Y, Zhang Q. Trichosanthin suppresses the proliferation of glioma cells by inhibiting LGR5 expression and the Wnt/beta-catenin signaling pathway. Oncol Rep. 2015;34:2845–52.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Bezivin C, Tomasi S, Lohezic-Le Devehat F, Boustie J. Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. Phytomedicine. 2003;10:499–503.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Schmidt ML, Kuzmanoff KL, Ling-Indeck L, Pezzuto JM. Betulinic acid induces apoptosis in human neuroblastoma cell lines. Eur J Cancer. 1997;33:2007–10.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Liao MH, Lin WC, Wen HC, Pu HF. Tithonia diversifolia and its main active component tagitinin C induce survivin inhibition and G2/M arrest in human malignant glioblastoma cells. Fitoterapia. 2011;82:331–41.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Dissanayake AA, Bejcek BE, Zhang CR, Nair MG. Sesquiterpenoid lactones in Tanacetum huronense inhibit human glioblastoma cell proliferation. Nat Prod Commun. 2016;11:579–82.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Ismail AM, Musa AM, Nasir T, Magaji MG, Jega YA, Ibrahim I. Anti-proliferative study and isolation of Ochna flavone from the ethyl acetate-soluble fraction of Ochna kibbiensis Hutch & Dalziel. Nat Prod Res. 2017;31:2149–52.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Fan Y, Xue W, Schachner M, Zhao W. Honokiol eliminates glioma/glioblastoma stem cell-like cells via JAK-STAT3 signaling and inhibits tumor progression by targeting epidermal growth factor receptor. Cancers. 2018;26:11.Google Scholar
  29. 29.
    Borawska MH, Naliwajko SK, Moskwa J, Markiewicz-Żukowska R, Puścion-Jakubik A, Soroczyńska J. Anti-proliferative and anti-migration effects of polish propolis combined with Hypericum perforatum L. on glioblastoma multiform cell line U87MG. BMC Complement Altern Med. 2016;16:367.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Schotterl S, Hubner M, Armento A, Veninga V, Wirsik NM, Bernatz S, Lentzen H, Mittelbronn M, Naumann U. Viscumins functionally modulate cell motility-associated gene expression. Int J Oncol. 2017;50:684–96.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116:205–19.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Khan M, Yu B, Rasul A, Al Shawi A, Yi F, Yang H, Ma T. Jaceosidin induces apoptosis in U87 glioblastoma cells through g2/m phase arrest. Evid Based Complement Alternat Med. 2012;2012:703034.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Wang Y, Tang H, Zhang Y, Li J, Li B, Gao Z, Wang X, Cheng G, Fei Z. Saponin B, a novel cytostatic compound purified from Anemone taipaiensis, induces apoptosis in a human glioblastoma cell line. Int J Mol Med. 2013;32:1077–84.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Li J, Tang H, Zhang Y, Tang C, Li B, Wang Y, Gao Z, Luo P, Yin A, Wang X, Cheng G, Fei Z. Saponin 1 induces apoptosis and suppresses NF-kappaB-mediated survival signaling in glioblastoma multiform (GBM). PLoS One. 2013;8:e81258.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Ji CC, Tang HF, Hu YY, Zhang Y, Zheng MH, Qin HY, Li SZ, Wang XY, Fei Z, Cheng G. Saponin 6 derived from Anemone taipaiensis induces U87 human malignant glioblastoma cell apoptosis via regulation of Fas and Bcl2 family proteins. Mol Med Rep. 2016;14:380–6.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Lee DY, Lee MK, Kim GS, Noh HJ, Lee MH. Brazilin inhibits growth and induces apoptosis in human glioblastoma cells. Molecules. 2013;18:2449–57.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Rooprai HK, Christidou M, Pilkington GJ. The potential for strategies using micronutrients and heterocyclic drugs to treat invasive gliomas. Acta Neurochir (Wien). 2003;145:683–90.CrossRefGoogle Scholar
  38. 38.
    Chang HF, Huang WT, Chen HJ, Yang LL. Apoptotic effects of gamma-mangostin from the fruit hull of Garcinia mangostana on human malignant glioma cells. Molecules. 2010;15:8953–66.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Wick W, Grimmel C, Wagenknecht B, Dichgans J, Weller M. Betulinic acid-induced apoptosis in glioma cells: a sequential requirement for new protein synthesis, formation of reactive oxygen species, and caspase processing. J Pharmacol Exp Ther. 1999;289:1306–12.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Kapoor H, Yadav N, Chopra M, Mahapatra SC, Agrawal V. Strong anti-tumorous potential of Nardostachys jatamansi rhizome extract on glioblastoma and in silico analysis of its molecular drug targets. Curr Cancer Drug Targets. 2017;17:74–88.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Eom KS, Kim HJ, So HS, Park R, Kim TY. Berberine induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction. Biol Pharm Bull. 2010;33:1644–9.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Giakoumettis D, Pourzitaki C, Vavilis T, Tsingotjidou A, Kyriakoudi A, Tsimidou M, Boziki M, Sioga A, Foroglou N, Kritis A. Calpain-dependent death in C6 Rat glioma cells, exhibiting a synergistic effect with temozolomide. Nutr Cancer. 2017.  https://doi.org/10.1080/01635581.2018.1506493.CrossRefGoogle Scholar
  43. 43.
    Mounira K, Nouha N, Imen M, Kamel G, Leila CG. Limoniastrum guyonianum extracts induce apoptosis via DNA damage, PARP cleavage and UHRF1 down-regulation in human glioma U373 cells. J Nat Prod. 2014;7:79–86.Google Scholar
  44. 44.
    de Souza PO, Bianchi SE, Figueiró F, Heimfarth L, Moresco KS, Gonçalves RM, Hoppe JB, Klein CP, Salbego CG, Gelain DP, Bassani VL, Filho AZ, Moreira JCF. Anticancer activity of flavonoids isolated from Achyrocline satureioides in gliomas cell lines. Toxicol In Vitro. 2018.  https://doi.org/10.1016/j.tiv.2018.04.013.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–6.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146:1029–39.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Polette M, Nawrocki-Raby B, Gilles C, Clavel C, Birembaut P. Tumor invasion and matrix metalloproteinases. Crit Rev Oncol Hematol. 2004;49:179–86.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Lin MT, Yen ML, Lin CY, Kuo ML. Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation. Mol Pharmacol. 2003;64:1029–36.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Freitas S, Costa S, Azevedo C, Carvalho G, Freire S, Barbosa P, Velozo E, Schaer R, Tardy M, Meyer R, Nascimento I. Flavonoids inhibit angiogenic cytokine production by human glioma cells. Phytother Res. 2011;25:916–21.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Zhang FJ, Yang JY, Mou YH, Sun BS, Ping YF, Wang JM, Bian XW, Wu CF. Inhibition of U-87 human glioblastoma cell proliferation and formyl peptide receptor function by oligomer procyanidins (F2) isolated from grape seeds. Chem Biol Interact. 2009;179:419–29.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Zheng HL, Yang J, Hou Y, Sun B, Zhang Q, Mou Y, Wand L, Wu C. Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1alpha in vitro. Int J Oncol. 2015;46:708–20.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    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.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Cui Y, Bai Y, Wang XD, Liu B, Zhao Z, Wang LS. Differential expression of miRNA in rat myocardial tissues under psychological and physical stress. Exp Ther Med. 2014;7:901–6.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Sun C, Yu Y, Wang L, Wu B, Xia L, Feng F, Ling Z, Wang S. Additive antiangiogenesis effect of ginsenoside Rg3 with low-dose metronomic temozolomide on rat glioma cells both in vivo and in vitro. J Exp Clin Cancer Res. 2016;35:32.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Elhag R, Mazzio EA, Soliman KF. The effect of silibinin in enhancing toxicity of temozolomide and etoposide in p53 and PTEN-mutated resistant glioma cell lines. Anticancer Res. 2015;35(3):1263–9.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Chakrabarti M, Ray SK. Synergistic anti-tumor actions of luteolin and silibinin prevented cell migration and invasion and induced apoptosis in glioblastoma SNB19 cells and glioblastoma stem cells. Brain Res. 2015;1629:85–93.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Chakrabarti M, Ray SK. Anti-tumor activities of luteolin and silibinin in glioblastoma cells: overexpression of miR-7-1-3p augmented luteolin and silibinin to inhibit autophagy and induce apoptosis in glioblastoma in vivo. Apoptosis. 2016;21(3):312–28.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Bai ZL, Tay V, Guo SZ, Ren J, Shu MG. Silibinin induced human glioblastoma cell apoptosis concomitant with autophagy through simultaneous inhibition of mTOR and YAP. Biomed Res Int. 2018;2018:6165192.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Verdura S, Cuyàs E, Llorach-Parés L, Pérez-Sánchez A, Micol V, Nonell-Canals A, Joven J, Valiente M, Sánchez-Martínez M, Bosch-Barrera J, Menendez JA. Silibinin is a direct inhibitor of STAT3. Food Chem Toxicol. 2018;116(Pt B):161–72.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Chang N, Ahn SH, Kong DS, Lee HW, Nam DH. The role of STAT3 in glioblastoma progression through dual influences on tumor cells and the immune microenvironment. Mol Cell Endocrinol. 2017;451:53–65.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Pérez-Sánchez A, Cuyàs E, Ruiz-Torres V, Agulló-Chazarra L, Verdura S, González-Álvarez I, Bermejo M, Joven J, Micol V, Bosch-Barrera J, Menendez JA. intestinal permeability study of clinically relevant formulations of silibinin in Caco-2 cell monolayers. Int J Mol Sci. 2019;20(7):1606.PubMedCentralCrossRefGoogle Scholar
  62. 62.
    Nico B, Ribatti D. Morpho-functional aspects of the blood brain barrier. Curr Drug Metab. 2012;13:50–60.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Schinkel AH. P-Glycoprotein, a gatekeeper in the bloodbrain barrier. Adv Drug Deliv Rev. 1999;36:179–94.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med. 2013;19:1584–96.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Lecuyer MA, Kebir H, Prat A. Glial influences on BBB functions and molecular players in immune cell trafficking. Biochim Biophys Acta. 2016;1862:472–82.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Zhao X, Chen R, Liu M, Feng J, Chen J, Hu K. Remodeling the blood-brain barrier microenvironment by natural products for brain tumor therapy. Acta Pharm Sin B. 2017;7:541–53.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    van Tellingen O, Yetkin-Arik B, de Gooijer MC, Wesseling P, Wurdinger T, de Vries HE. Overcoming the blood-brain tumor barrier for effective glioblastoma treatment. Drug Resist Updat. 2015;19:1–12.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Jacobs VL, Landry RP, Liu Y, Romero-Sandoval EA, De Leo JA. Propentofylline decreases tumor growth in a rodent model of glioblastoma multiform by a direct mechanism on microglia. Neuro Oncol. 2012;14:119–31.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Staniforth V, Wang SY, Shyur LF, Yang NS. Shikonins, phytocompounds from Lithospermum erythrorhizon, inhibit the transcriptional activation of human tumor necrosis factor alpha promoter in vivo. J Biol Chem. 2004;279:5877–85.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Wang L, Li Z, Zhang X, Wang S, Zhu C, Miao J, Chen L, Cui L, Qiao H. Protective effect of shikonin in experimental ischemic stroke: attenuated TLR4, p-p38MAPK, NF-kappaB, TNF-alpha and MMP-9 expression, up-regulated claudin-5 expression, ameliorated BBB permeability. Neurochem Res. 2014;39:97–106.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Zhang FY, Hu Y, Que ZY, Wang P, Liu YH, Wang ZH, Xue YX. Shikonin inhibits the migration and invasion of human glioblastoma cells by targeting phosphorylated beta-catenin and phosphorylated PI3K/Akt: a potential mechanism for the anti-glioma efficacy of a traditional chinese herbal medicine. Int J Mol Sci. 2015;16:23823–48.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Wei H, Wang S, Zhen L, Yang Q, Wu Z, Lei X, Lv J, Xiong L, Xue R. Resveratrol attenuates the blood-brain barrier dysfunction by regulation of the MMP-9/TIMP-1 balance after cerebral ischemia reperfusion in rats. J Mol Neurosci. 2015;55:872–9.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    He L, Zhao C, Yan M, Zhang LY, Xia YZ. Inhibition of P-glycoprotein function by procyanidin on blood-brain barrier. Phytother Res. 2009;23:933–7.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Wu H, Liu Q, Cai T, Chen YD, Wang ZF. Induction ofmicroRNA-146a is involved in curcumin-mediated enhancement of temozolomide cytotoxicity against human glioblastoma. Mole Med Rep. 2015;12:5461–6.CrossRefGoogle Scholar
  75. 75.
    Waterland RA, Jirtle RL. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition. 2004;20:63–8.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Yang R, Yi L, Dong Z, Ouyang Q, Zhou J, Pang Y, Wu Y, Xu L, Cui H. Tigecycline inhibits glioma growth by regulating microRNA-199b-5p-HES1-AKT pathway. Mol Cancer Ther. 2016;15:421–9.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Yan X, Liang H, Deng T, et al. The identification of novel targets of miR-16 and characterization of their biological functions in cancer cells. Mol Cancer. 2013;12:92.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Tezcan G, Tunca B, Bekar A, et al. Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression. Am J Cancer Res. 2014;4:572–90.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Aqeilan RI, Calin GA, Croce CM. miR-15a and miR-16-1 in cancer: discovery, function and future perspectives. Cell Death Differ. 2010;17:215–20.CrossRefGoogle Scholar
  80. 80.
    Zhu Y, Xia Y, Niu H, Chen Y. MiR-16 induced the suppression of cell apoptosis while promote proliferation in esophageal squamous cell carcinoma. Cell Physiol Biochem. 2014;33:1340–8.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Yang TQ, Lu XJ, Wu TF, Ding DD, Zhao ZH, Chen GL, Xie XS, Li B, Wei YX, Guo LC, et al. MicroRNA-16 inhibits glioma cell growth and invasion through suppression of BCL2 and the nuclear factor-kappaB1/MMP9 signaling pathway. Cancer Sci. 2014;105:265–71.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Zhang Y, Chao T, Li R, Liu W, Chen Y, Yan X, et al. MicroRNA-128 inhibits glioma cells proliferation by targeting transcription factor E2F3a. J Mol Med. 2009;87:43–51.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Feng Z, Zhang C, Wu R, Hu W. Tumor suppressor p53 meets microRNAs. J Mol Cell Biol. 2011;3:44–50.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Nan WU, Guo-cai WU, Rong HU, Mei LI, Hua FENG. Ginsenoside Rh2 inhibits glioma cell proliferation by targeting microRNA-128. Acta Pharmacol Sin. 2011;32:345–53.CrossRefGoogle Scholar
  85. 85.
    Tunca B, Tezcan G, Cecener G, Egeli U, Ak S, Malyer H, Tumen G, Bilir A. Olea europaea leaf extract alters microRNA expression in human glioblastoma cells. J Cancer Res Clin Oncol. 2012;138:1831–44.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Tezcan G, Tunca B, Bekar A, et al. Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression. Am J Cancer Res. 2014;4:572–90.PubMedPubMedCentralGoogle Scholar
  87. 87.
    Tezcan G, Tunca B, Bekaretal A. Ficus carica latex prevents invasion through induction of let-7d expression in GBM cell lines. Cell Mol Neurobiol. 2015;35:175–87.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Liu J, Qu CB, Xue YX, Li Z, Wang P, Liu YH. MIR143 enhances the antitumor activity of shikonin by targeting BAG3 expression in human glioblastoma stem cells. Biochem Biophys Res Commun. 2015;468:105–12.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Yang F, Nam S, Brown CE, Zhao R, Starr R. A novel berbamine derivative inhibits cell viability and induces apoptosis in cancer stem-like cells of human glioblastoma, via up-regulation of miRNA-4284 and JNK/AP-1 signaling. PLoS One. 2014;9:e94443.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Li W, Yang W, Liu Y, Chen S, Chin S, Qi X, Zhao Y, Liu H, Wang J, Mei X, Huang P, Xu D. MicroRNA-378 enhances inhibitory effect of curcumin on glioblastoma. Oncotarget. 2017;8:73938–46.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Agbarya A, Ruimi N, Epelbaum R, Ben-Arye E, Mahajna J. Natural products as potential cancer therapy enhancers: a preclinical update. SAGE Open Med. 2014;2:2050312114546924.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet. 2000;9:2395–402.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Baylin SB, Ohm JE. Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addiction? Nat Rev Cancer. 2006;6:107–16.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Jianqing MA, Peng Y, Li X. Differential expression of Agouti mRNA and its coding protein in viscera of goat with different coat color. Indian J Anim Res. 2016;50:690–4.Google Scholar
  95. 95.
    Vanden BW. Epigenetic impact of dietary polyphenols in cancer chemoprevention: lifelong remodeling of our epigenomes. Pharmacol Res. 2012;65:565–76.CrossRefGoogle Scholar
  96. 96.
    Hardy TM, Tollefsbol TO. Epigenetic diet: impact on the epigenome and cancer. Epigenomics. 2011;3:503–18.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Wu B, Yao X, Nie X, Xu R. Epigenetic reactivation of RANK in glioblastoma cells by curcumin: involvement of STAT3 inhibition. DNA Cell Biol. 2013;32:292–7.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Skała E, Toma M, Kowalczyk T, Sliwinski T, Sitarek P. Rhaponticum carthamoides transformed root extract inhibits human glioma cells viability, induces double strand DNA damage, H2A.X phosphorylation, and PARP1 cleavage. Cytotechnology. 2018;70:1585–94.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Marks PA, Xu WS. Histone deacetylase inhibitors: potential in cancer therapy. J Cell Biochem. 2009;107:600–8.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Kelly WK, O’Connor OA, Marks PA. Histone deacetylase inhibitors: from target to clinical trials. Expert Opin Invest Drugs. 2002;11:1695–713.CrossRefGoogle Scholar
  101. 101.
    Esteller M, Herman JG. Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol. 2002;196:1–7.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Ellis L, Atadja PW, Johnstone RW. Epigenetics in cancer: targeting chromatin modifications. Mol Cancer Ther. 2009;8:1409–20.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Duvic M, Talpur R, Ni X, Zhang C, Hazarika P, et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood. 2007;109:31–9.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Campas-Moya C. Romidepsin for the treatment of cutaneous T-cell lymphoma. Drugs Today. 2009;45:787–95.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Vargas JE, Filippi-Chiela EC, Suhre T, Kipper FC, Bonatto D, Lenz G. Inhibition of HDAC increases the senescence induced by natural polyphenols in glioma cells. Biochem Cell Biol. 2014;92:297–304.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Jiao Y, Killela PJ, Reitman ZJ, Rasheed A, Heaphy CM, de Wilde RF, et al. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget. 2012;3:710–22.CrossRefGoogle Scholar
  107. 107.
    Ebrahimi A, Skardelly M, Bonzheim I, Ott I, Mühleisen H, Eckert F, Tabatabai G, Schittenhelm J. ATRX immunostaining predicts IDH and H3F3A status in gliomas. Acta Neuropathol Commun. 2016;4:60.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, Koboldt DC, et al. The origin and evolution of mutations in acute myeloid leukemia. Cell. 2012;2012:264–78.CrossRefGoogle Scholar
  109. 109.
    Lu C, Venneti S, Akalin A, Fang F, Ward PS, DeMatteo RG, et al. Induction of sarcomas by mutant IDH2. Genes Dev. 2013;27:1986–98.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Dong Z, Abbas MN, Kausar S, Yang J, Li L, Tan L, Cui H. Biological functions and molecular mechanisms of antibiotic tigecycline in the treatment of cancers. Int J Mol Sci. 2019;20:3577.PubMedCentralCrossRefGoogle Scholar
  111. 111.
    Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462:739–44.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell. 2011;19:17–30.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Chowdhury R, Yeoh KK, Tian YM, Hillringhaus L, Bagg EA, Rose NR, et al. The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 2011;12:463–9.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130:722–31.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Sharma H. Development of novel therapeutics targeting isocitrate dehydrogenase mutations in cancer. Curr Top Med Chem. 2018;18:505–24.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Silkworm Genome BiologySouthwest UniversityChongqingChina
  2. 2.Engineering Research Center for Cancer Biomedical and Translational MedicineSouthwest UniversityChongqingChina
  3. 3.Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative MedicineSouthwest UniversityChongqingChina
  4. 4.Medical Research InstituteSouthwest UniversityChongqingChina

Personalised recommendations