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Epigenetic Targeting of Vascular Endothelial Growth Factor (VEGF) Receptors

  • Steven G. Gray
Reference work entry

Abstract

Signaling through VEGF receptors is not limited to the regulation of angiogenesis. Emerging data now links VEGF as a critical survival factor in carcinogenesis, with additional roles in immune surveillance and cancer stem cells. While a significant effort has been made within the pharmaceutical space to directly target VEGF signaling, results have been mixed. Research has shown that both VEGF and its associated receptors are epigenetically regulated and as such may be targetable through agents that inhibit the epigenetic regulatory machinery.

Keywords

VEGF VEGFR Neuropilins Semaphorins Posttranslational modifications Dendritic cells Cancer stem cells Histone deacetylases Nutritional bioactives Epigenetic priming 

List of Abbreviations

BET

Bromodomain and extra-terminal domain

BRD

Bromodomain-containing protein

DCR

Disease control rate

EZH2

Enhancer of zeste, drosophila, homolog 2

HDAC

Histone deacetylase

KAT

Lysine-specific acetyltransferase

KDM

Lysine-specific demethylase

KMT

Lysine-specific methyltransferase

NGS

Next-generation sequencing

ORR

Objective response rate

OS

Overall survival

PFS

Progression-free survival

PRC2

Polycomb repressive complex 2

PTM

Posttranslational modification

VEGF

Vascular endothelial growth factor

References

  1. Albuquerque RJ, Hayashi T, Cho WG, Kleinman ME, Dridi S, Takeda A, Baffi JZ, Yamada K, Kaneko H, Green MG, Chappell J, Wilting J, Weich HA, Yamagami S, Amano S, Mizuki N, Alexander JS, Peterson ML, Brekken RA, Hirashima M, Capoor S, Usui T, Ambati BK, Ambati J (2009) Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat Med 15:1023–1030CrossRefPubMedPubMedCentralGoogle Scholar
  2. Baird AM, Gray SG, O’Byrne KJ (2011) IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF. Eur J Cancer 47:1908–1918Google Scholar
  3. Barr MP, Gray SG, Gately K, Hams E, Fallon PG, Davies AM, Richard DJ, Pidgeon GP, O’Byrne KJ (2015a) Vascular endothelial growth factor is an autocrine growth factor, signaling through neuropilin-1 in non-small cell lung cancer. Mol Cancer 14:45Google Scholar
  4. Barr MP, O’Byrne KJ, Al-Sarraf N, Gray SG (2015b) VEGF-mediated cell survival in non-small-cell lung cancer: implications for epigenetic targeting of VEGF receptors as a therapeutic approach. Epigenomics 7:897–910Google Scholar
  5. Beck B, Driessens G, Goossens S, Youssef KK, Kuchnio A, Caauwe A, Sotiropoulou PA, Loges S, Lapouge G, Candi A, Mascre G, Drogat B, Dekoninck S, Haigh JJ, Carmeliet P, Blanpain C (2011) A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours. Nature 478:399–403CrossRefPubMedGoogle Scholar
  6. Bid HK, Phelps DA, Xaio L, Guttridge DC, Lin J, London C, Baker LH, Mo X, Houghton PJ (2016) The bromodomain BET inhibitor JQ1 suppresses tumor angiogenesis in models of childhood sarcoma. Mol Cancer Ther 15:1018–1028CrossRefPubMedPubMedCentralGoogle Scholar
  7. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2:401–404CrossRefPubMedGoogle Scholar
  8. Charrier C, Clarhaut J, Gesson JP, Estiu G, Wiest O, Roche J, Bertrand P (2009) Synthesis and modeling of new benzofuranone histone deacetylase inhibitors that stimulate tumor suppressor gene expression. J Med Chem 52:3112–3115CrossRefPubMedGoogle Scholar
  9. Chatterjee S, Bhattacharjee B (2012) Use of natural molecules as anti-angiogenic inhibitors for vascular endothelial growth factor receptor. Bioinformation 8:1249–1254CrossRefPubMedPubMedCentralGoogle Scholar
  10. Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B, Hein A, Rote NS, Cope LM, Snyder A, Makarov V, Budhu S, Slamon DJ, Wolchok JD, Pardoll DM, Beckmann MW, Zahnow CA, Merghoub T, Chan TA, Baylin SB, Strick R (2016) Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 164:1073CrossRefPubMedGoogle Scholar
  11. Ciura J, Jagodzinski PP (2010) Butyrate increases the formation of anti-angiogenic vascular endothelial growth factor variants in human lung microvascular endothelial cells. Mol Biol Rep 37:3729–3734CrossRefPubMedGoogle Scholar
  12. Courau T, Nehar-Belaid D, Florez L, Levacher B, Vazquez T, Brimaud F, Bellier B, Klatzmann D (2016) TGF-beta and VEGF cooperatively control the immunotolerant tumor environment and the efficacy of cancer immunotherapies. JCI Insight 1:e85974CrossRefPubMedPubMedCentralGoogle Scholar
  13. Deroanne CF, Bonjean K, Servotte S, Devy L, Colige A, Clausse N, Blacher S, Verdin E, Foidart JM, Nusgens BV, Castronovo V (2002) Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene 21:427–436CrossRefPubMedGoogle Scholar
  14. Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS (2003) Tea polyphenol (−)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 63:7563–7570PubMedGoogle Scholar
  15. Gagnon ML, Bielenberg DR, Gechtman Z, Miao HQ, Takashima S, Soker S, Klagsbrun M (2000) Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: in vivo expression and antitumor activity. Proc Natl Acad Sci U S A 97:2573–2578CrossRefPubMedPubMedCentralGoogle Scholar
  16. Geng J, Li X, Zhou Z, Wu CL, Dai M, Bai X (2015) EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer. Cancer Lett 359:275–287CrossRefPubMedGoogle Scholar
  17. Gertz M, Nguyen GT, Fischer F, Suenkel B, Schlicker C, Franzel B, Tomaschewski J, Aladini F, Becker C, Wolters D, Steegborn C (2012) A molecular mechanism for direct sirtuin activation by resveratrol. PLoS One 7:e49761CrossRefPubMedPubMedCentralGoogle Scholar
  18. Goel HL, Mercurio AM (2013) VEGF targets the tumour cell. Nat Rev Cancer 13:871–882CrossRefPubMedPubMedCentralGoogle Scholar
  19. Goldman CK, Kendall RL, Cabrera G, Soroceanu L, Heike Y, Gillespie GY, Siegal GP, Mao X, Bett AJ, Huckle WR, Thomas KA, Curiel DT (1998) Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate. Proc Natl Acad Sci U S A 95:8795–8800CrossRefPubMedPubMedCentralGoogle Scholar
  20. Gray SG, Ekström TJ (2001) The human histone deacetylase family. Exp Cell Res 262:75–83Google Scholar
  21. Gyorffy B, Surowiak P, Budczies J, Lanczky A (2013) Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One 8:e82241CrossRefPubMedPubMedCentralGoogle Scholar
  22. Hall RD, Le TM, Haggstrom DE, Gentzler RD (2015) Angiogenesis inhibition as a therapeutic strategy in non-small cell lung cancer (NSCLC). Transl Lung Cancer Res 4:515–523PubMedPubMedCentralGoogle Scholar
  23. Hartsough EJ, Meyer RD, Chitalia V, Jiang Y, Marquez VE, Zhdanova IV, Weinberg J, Costello CE, Rahimi N (2013) Lysine methylation promotes VEGFR-2 activation and angiogenesis. Sci Signal 6:ra104CrossRefPubMedPubMedCentralGoogle Scholar
  24. He L, Zhang E, Shi J, Li X, Zhou K, Zhang Q, Le AD, Tang X (2013) (−)-Epigallocatechin-3-gallate inhibits human papillomavirus (HPV)-16 oncoprotein-induced angiogenesis in non-small cell lung cancer cells by targeting HIF-1alpha. Cancer Chemother Pharmacol 71:713–725CrossRefPubMedGoogle Scholar
  25. Hodi FS, Lawrence D, Lezcano C, Wu X, Zhou J, Sasada T, Zeng W, Giobbie-Hurder A, Atkins MB, Ibrahim N, Friedlander P, Flaherty KT, Murphy GF, Rodig S, Velazquez EF, Mihm MC Jr, Russell S, Dipiro PJ, Yap JT, Ramaiya N, Van Den Abbeele AD, Gargano M, Mcdermott D (2014) Bevacizumab plus ipilimumab in patients with metastatic melanoma. Cancer Immunol Res 2:632–642CrossRefPubMedPubMedCentralGoogle Scholar
  26. Hong TM, Chen YL, Wu YY, Yuan A, Chao YC, Chung YC, Wu MH, Yang SC, Pan SH, Shih JY, Chan WK, Yang PC (2007) Targeting neuropilin 1 as an antitumor strategy in lung cancer. Clin Cancer Res 13:4759–4768CrossRefPubMedGoogle Scholar
  27. Hong S, Tan M, Wang S, Luo S, Chen Y, Zhang L (2015) Efficacy and safety of angiogenesis inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis. J Cancer Res Clin Oncol 141:909–921CrossRefPubMedGoogle Scholar
  28. Hoos A (2016) Development of immuno-oncology drugs – from CTLA4 to PD1 to the next generations. Nat Rev Drug Discov 15:235–247CrossRefPubMedGoogle Scholar
  29. Horinouchi H (2016) Anti-vascular endothelial growth factor therapies at the crossroads: linifanib for non-small cell lung cancer. Transl Lung Cancer Res 5:78–81PubMedPubMedCentralGoogle Scholar
  30. Huang M, Qiu Q, Xiao Y, Zeng S, Zhan M, Shi M, Zou Y, Ye Y, Liang L, Yang X, Xu H (2016) BET bromodomain suppression inhibits VEGF-induced angiogenesis and vascular permeability by blocking VEGFR2-mediated activation of PAK1 and eNOS. Sci Rep 6:23770CrossRefPubMedPubMedCentralGoogle Scholar
  31. Jiang LL, Zhou SJ, Zhang XM, Chen HQ, Liu W (2016) Sulforaphane suppresses in vitro and in vivo lung tumorigenesis through downregulation of HDAC activity. Biomed Pharmacother 78:74–80CrossRefPubMedGoogle Scholar
  32. Jiao D, Wang J, Lu W, Tang X, Chen J, Mou H, Chen QY (2016) Curcumin inhibited HGF-induced EMT and angiogenesis through regulating c-Met dependent PI3K/Akt/mTOR signaling pathways in lung cancer. Mol Ther Oncolytics 3:16018CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kawakami T, Tokunaga T, Hatanaka H, Kijima H, Yamazaki H, Abe Y, Osamura Y, Inoue H, Ueyama Y, Nakamura M (2002) Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma. Cancer 95:2196–2201CrossRefPubMedGoogle Scholar
  34. Kim MS, Kwon HJ, Lee YM, Baek JH, Jang JE, Lee SW, Moon EJ, Kim HS, Lee SK, Chung HY, Kim CW, Kim KW (2001) Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med 7:437–443CrossRefPubMedGoogle Scholar
  35. Kim SH, Kim KW, Jeong JW (2007) Inhibition of hypoxia-induced angiogenesis by sodium butyrate, a histone deacetylase inhibitor, through hypoxia-inducible factor-1alpha suppression. Oncol Rep 17:793–797PubMedGoogle Scholar
  36. Kim DH, Sung B, Kang YJ, Hwang SY, Kim MJ, Yoon JH, Im E, Kim ND (2015) Sulforaphane inhibits hypoxia-induced HIF-1alpha and VEGF expression and migration of human colon cancer cells. Int J Oncol 47:2226–2232CrossRefPubMedGoogle Scholar
  37. Kimura Y, Okuda H (2001) Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice. J Nutr 131:1844–1849CrossRefPubMedGoogle Scholar
  38. Kimura Y, Sumiyoshi M (2016) Resveratrol prevents tumor growth and metastasis by inhibiting lymphangiogenesis and M2 macrophage activation and differentiation in tumor-associated macrophages. Nutr Cancer 68:667–678CrossRefPubMedGoogle Scholar
  39. Koch S, Tugues S, Li X, Gualandi L, Claesson-Welsh L (2011) Signal transduction by vascular endothelial growth factor receptors. Biochem J 437:169–183CrossRefPubMedGoogle Scholar
  40. Kubota K, Ichinose Y, Scagliotti G, Spigel D, Kim JH, Shinkai T, Takeda K, Kim SW, Hsia TC, Li RK, Tiangco BJ, Yau S, Lim WT, Yao B, Hei YJ, Park K (2014) Phase III study (MONET1) of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC): Asian subgroup analysis. Ann Oncol 25:529–536CrossRefPubMedGoogle Scholar
  41. Kunizaki M, Hamamoto R, Silva FP, Yamaguchi K, Nagayasu T, Shibuya M, Nakamura Y, Furukawa Y (2007) The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3. Cancer Res 67:10759–10765CrossRefPubMedGoogle Scholar
  42. Kuntz KW, Campbell JE, Keilhack H, Pollock RM, Knutson SK, Porter-Scott M, Richon VM, Sneeringer CJ, Wigle TJ, Allain CJ, Majer CR, Moyer MP, Copeland RA, Chesworth R (2016) The importance of being me: magic methyls, methyltransferase inhibitors, and the discovery of tazemetostat. J Med Chem 59:1556–1564CrossRefPubMedGoogle Scholar
  43. Kurschat P, Bielenberg D, Rossignol-Tallandier M, Stahl A, Klagsbrun M (2006) Neuron restrictive silencer factor NRSF/REST is a transcriptional repressor of neuropilin-1 and diminishes the ability of semaphorin 3A to inhibit keratinocyte migration. J Biol Chem 281:2721–2729CrossRefPubMedGoogle Scholar
  44. Li X, Feng Y, Liu J, Feng X, Zhou K, Tang X (2013) Epigallocatechin-3-gallate inhibits IGF-I-stimulated lung cancer angiogenesis through downregulation of HIF-1alpha and VEGF expression. J Nutrigenet Nutrigenomics 6:169–178CrossRefPubMedGoogle Scholar
  45. Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, Topper MJ, Luo J, Connolly RM, Azad NS, Stearns V, Pardoll DM, Davidson N, Jones PA, Slamon DJ, Baylin SB, Zahnow CA, Ahuja N (2014) Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 5:587–598PubMedPubMedCentralGoogle Scholar
  46. Li YL, Zhao H, Ren XB (2016) Relationship of VEGF/VEGFR with immune and cancer cells: staggering or forward? Cancer Biol Med 13:206–214CrossRefPubMedPubMedCentralGoogle Scholar
  47. Lin SS, Lai KC, Hsu SC, Yang JS, Kuo CL, Lin JP, Ma YS, Wu CC, Chung JG (2009) Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and -9 and Vascular Endothelial Growth Factor (VEGF). Cancer Lett 285:127–133CrossRefPubMedGoogle Scholar
  48. Loginov VI, Dmitriev AA, Senchenko VN, Pronina IV, Khodyrev DS, Kudryavtseva AV, Krasnov GS, Gerashchenko GV, Chashchina LI, Kazubskaya TP, Kondratieva TT, Lerman MI, Angeloni D, Braga EA, Kashuba VI (2015) Tumor suppressor function of the SEMA3B Gene in human lung and renal cancers. PLoS One 10:e0123369CrossRefPubMedPubMedCentralGoogle Scholar
  49. Lu C, Han HD, Mangala LS, Ali-Fehmi R, Newton CS, Ozbun L, Armaiz-Pena GN, Hu W, Stone RL, Munkarah A, Ravoori MK, Shahzad MM, Lee JW, Mora E, Langley RR, Carroll AR, Matsuo K, Spannuth WA, Schmandt R, Jennings NB, Goodman BW, Jaffe RB, Nick AM, Kim HS, Guven EO, Chen YH, Li LY, Hsu MC, Coleman RL, Calin GA, Denkbas EB, Lim JY, Lee JS, Kundra V, Birrer MJ, Hung MC, Lopez-Berestein G, Sood AK (2010) Regulation of tumor angiogenesis by EZH2. Cancer Cell 18:185–197CrossRefPubMedPubMedCentralGoogle Scholar
  50. Miki K, Shimizu E, Yano S, Tani K, Sone S (2001) Demethylation by 5-aza-2′-deoxycytidine (5-azadC) of p16INK4A gene results in downregulation of vascular endothelial growth factor expression in human lung cancer cell lines. Oncol Res 12:335–342CrossRefPubMedGoogle Scholar
  51. Miller-Kasprzak E, Jagodzinski PP (2008) 5-Aza-2′-deoxycytidine increases the expression of anti-angiogenic vascular endothelial growth factor 189b variant in human lung microvascular endothelial cells. Biomed Pharmacother 62:158–163CrossRefPubMedGoogle Scholar
  52. Moon CY, Ku CR, Cho YH, Lee EJ (2012) Protocatechuic aldehyde inhibits migration and proliferation of vascular smooth muscle cells and intravascular thrombosis. Biochem Biophys Res Commun 423:116–121CrossRefPubMedGoogle Scholar
  53. Nakagawa-Yagi Y, Sato Y, Matsumoto E, Nakatsuka S, Sakaki T, Muramatsu Y, Hara T, Aigaki T (2012) Pharmacological modulation of histone demethylase activity by a small molecule isolated from subcritical water extracts of Sasa senanensis leaves prolongs the lifespan of Drosophila melanogaster. BMC Complement Altern Med 12:101CrossRefPubMedPubMedCentralGoogle Scholar
  54. Nishijima N, Seike M, Soeno C, Chiba M, Miyanaga A, Noro R, Sugano T, Matsumoto M, Kubota K, Gemma A (2016) miR-200/ZEB axis regulates sensitivity to nintedanib in non-small cell lung cancer cells. Int J Oncol 48:937–944CrossRefPubMedPubMedCentralGoogle Scholar
  55. O’Byrne KJ, Barr MP, Gray SG (2011) The role of epigenetics in resistance to Cisplatin chemotherapy in lung cancer. Cancers (Basel) 3:1426–1453Google Scholar
  56. Oh SY, Seok JY, Choi YS, Lee SH, Bae JS, Lee YM (2015) The histone methyltransferase inhibitor BIX01294 inhibits HIF-1alpha stability and angiogenesis. Mol Cell 38:528–534CrossRefGoogle Scholar
  57. Parker MW, Linkugel AD, Goel HL, Wu T, Mercurio AM, Vander Kooi CW (2015) Structural basis for VEGF-C binding to neuropilin-2 and sequestration by a soluble splice form. Structure 23:677–687CrossRefPubMedPubMedCentralGoogle Scholar
  58. Patnaik A, Lorusso PM, Messersmith WA, Papadopoulos KP, Gore L, Beeram M, Ramakrishnan V, Kim AH, Beyer JC, Mason Shih L, Darbonne WC, Xin Y, Yu R, Xiang H, Brachmann RK, Weekes CD (2014) A phase Ib study evaluating MNRP1685A, a fully human anti-NRP1 monoclonal antibody, in combination with bevacizumab and paclitaxel in patients with advanced solid tumors. Cancer Chemother Pharmacol 73:951–960CrossRefPubMedGoogle Scholar
  59. Pecot CV, Rupaimoole R, Yang D, Akbani R, Ivan C, Lu C, Wu S, Han HD, Shah MY, Rodriguez-Aguayo C, Bottsford-Miller J, Liu Y, Kim SB, Unruh A, Gonzalez-Villasana V, Huang L, Zand B, Moreno-Smith M, Mangala LS, Taylor M, Dalton HJ, Sehgal V, Wen Y, Kang Y, Baggerly KA, Lee JS, Ram PT, Ravoori MK, Kundra V, Zhang X, Ali-Fehmi R, Gonzalez-Angulo AM, Massion PP, Calin GA, Lopez-Berestein G, Zhang W, Sood AK (2013) Tumour angiogenesis regulation by the miR-200 family. Nat Commun 4:2427CrossRefPubMedPubMedCentralGoogle Scholar
  60. Philibert RA, Sears RA, Powers LS, Nash E, Bair T, Gerke AK, Hassan I, Thomas CP, Gross TJ, Monick MM (2012) Coordinated DNA methylation and gene expression changes in smoker alveolar macrophages: specific effects on VEGF receptor 1 expression. J Leukoc Biol 92:621–631CrossRefPubMedPubMedCentralGoogle Scholar
  61. Rahimi N, Costello CE (2015) Emerging roles of post-translational modifications in signal transduction and angiogenesis. Proteomics 15:300–309CrossRefPubMedGoogle Scholar
  62. Rao M, Chinnasamy N, Hong JA, Zhang Y, Zhang M, Xi S, Liu F, Marquez VE, Morgan RA, Schrump DS (2011) Inhibition of histone lysine methylation enhances cancer-testis antigen expression in lung cancer cells: implications for adoptive immunotherapy of cancer. Cancer Res 71:4192–4204CrossRefPubMedPubMedCentralGoogle Scholar
  63. Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, Von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, Novello S (2014) Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol 15:143–155CrossRefPubMedGoogle Scholar
  64. Riquelme E, Suraokar M, Behrens C, Lin HY, Girard L, Nilsson MB, Simon G, Wang J, Coombes KR, Lee JJ, Hong WK, Heymach J, Minna JD, Wistuba II (2014) VEGF/VEGFR-2 upregulates EZH2 expression in lung adenocarcinoma cells and EZH2 depletion enhances the response to platinum-based and VEGFR-2-targeted therapy. Clin Cancer Res 20:3849–3861CrossRefPubMedPubMedCentralGoogle Scholar
  65. Sahin E, Baycu C, Koparal AT, Burukoglu Donmez D, Bektur E (2016) Resveratrol reduces IL-6 and VEGF secretion from co-cultured A549 lung cancer cells and adipose-derived mesenchymal stem cells. Tumour Biol 37:7573–7582CrossRefPubMedGoogle Scholar
  66. Sakamoto Y, Terashita N, Muraguchi T, Fukusato T, Kubota S (2013) Effects of epigallocatechin-3-gallate (EGCG) on A549 lung cancer tumor growth and angiogenesis. Biosci Biotechnol Biochem 77:1799–1803CrossRefPubMedGoogle Scholar
  67. Sawa H, Murakami H, Ohshima Y, Murakami M, Yamazaki I, Tamura Y, Mima T, Satone A, Ide W, Hashimoto I, Kamada H (2002) Histone deacetylase inhibitors such as sodium butyrate and trichostatin A inhibit vascular endothelial growth factor (VEGF) secretion from human glioblastoma cells. Brain Tumor Pathol 19:77–81CrossRefPubMedGoogle Scholar
  68. Scagliotti GV, Vynnychenko I, Park K, Ichinose Y, Kubota K, Blackhall F, Pirker R, Galiulin R, Ciuleanu TE, Sydorenko O, Dediu M, Papai-Szekely Z, Banaclocha NM, Mccoy S, Yao B, Hei YJ, Galimi F, Spigel DR (2012) International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1. J Clin Oncol 30:2829–2836CrossRefPubMedGoogle Scholar
  69. Shankar S, Marsh L, Srivastava RK (2013) EGCG inhibits growth of human pancreatic tumors orthotopically implanted in Balb C nude mice through modulation of FKHRL1/FOXO3a and neuropilin. Mol Cell Biochem 372:83–94CrossRefPubMedGoogle Scholar
  70. Shi J, Vakoc CR (2014) The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol Cell 54:728–736CrossRefPubMedGoogle Scholar
  71. Shi J, Liu F, Zhang W, Liu X, Lin B, Tang X (2015) Epigallocatechin-3-gallate inhibits nicotine-induced migration and invasion by the suppression of angiogenesis and epithelial-mesenchymal transition in non-small cell lung cancer cells. Oncol Rep 33:2972–2980CrossRefPubMedGoogle Scholar
  72. Sinclair DA, Guarente L (2014) Small-molecule allosteric activators of sirtuins. Annu Rev Pharmacol Toxicol 54:363–380CrossRefPubMedGoogle Scholar
  73. Teiten MH, Dicato M, Diederich M (2013) Curcumin as a regulator of epigenetic events. Mol Nutr Food Res 57:1619–1629CrossRefPubMedGoogle Scholar
  74. Tomizawa Y, Sekido Y, Kondo M, Gao B, Yokota J, Roche J, Drabkin H, Lerman MI, Gazdar AF, Minna JD (2001) Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B. Proc Natl Acad Sci U S A 98:13954–13959CrossRefPubMedPubMedCentralGoogle Scholar
  75. Tsai HC, Li H, Van Neste L, Cai Y, Robert C, Rassool FV, Shin JJ, Harbom KM, Beaty R, Pappou E, Harris J, Yen RW, Ahuja N, Brock MV, Stearns V, Feller-Kopman D, Yarmus LB, Lin YC, Welm AL, Issa JP, Minn I, Matsui W, Jang YY, Sharkis SJ, Baylin SB, Zahnow CA (2012) Transient low doses of DNA-demethylating agents exert durable antitumor effects on hematological and epithelial tumor cells. Cancer Cell 21:430–446CrossRefPubMedPubMedCentralGoogle Scholar
  76. Tung YT, Chen HL, Lai CW, Shen CJ, Lai YW, Chen CM (2011) Curcumin reduces pulmonary tumorigenesis in vascular endothelial growth factor (VEGF)-overexpressing transgenic mice. Mol Nutr Food Res 55:1036–1043CrossRefPubMedGoogle Scholar
  77. Tung YT, Chen HL, Lee CY, Chou YC, Lee PY, Tsai HC, Lin YL, Chen CM (2013) Active component of Danshen (Salvia miltiorrhiza Bunge), Tanshinone I, attenuates lung tumorigenesis via inhibitions of VEGF, Cyclin A, and Cyclin B expressions. Evid Based Complement Alternat Med 2013:319247PubMedPubMedCentralGoogle Scholar
  78. Wallin JJ, Bendell JC, Funke R, Sznol M, Korski K, Jones S, Hernandez G, Mier J, He X, Hodi FS, Denker M, Leveque V, Canamero M, Babitski G, Koeppen H, Ziai J, Sharma N, Gaire F, Chen DS, Waterkamp D, Hegde PS, Mcdermott DF (2016) Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat Commun 7:12624CrossRefPubMedPubMedCentralGoogle Scholar
  79. Wang S, Yang Z, Wang Z (2015) Are VEGFR-TKIs effective or safe for patients with advanced non-small cell lung cancer? Oncotarget 6:18206–18223PubMedPubMedCentralGoogle Scholar
  80. Wang X, Zhao H, Lv L, Bao L, Han S (2016) Prognostic significance of EZH2 expression in non-small cell lung cancer: a meta-analysis. Sci Rep 6:19239CrossRefPubMedPubMedCentralGoogle Scholar
  81. Woods DM, Sodre AL, Villagra A, Sarnaik A, Sotomayor EM, Weber J (2015) HDAC inhibition upregulates PD-1 ligands in melanoma and augments immunotherapy with PD-1 blockade. Cancer Immunol Res 3:1375–1385CrossRefPubMedPubMedCentralGoogle Scholar
  82. Wrangle J, Wang W, Koch A, Easwaran H, Mohammad HP, Vendetti F, Vancriekinge W, Demeyer T, Du Z, Parsana P, Rodgers K, Yen RW, Zahnow CA, Taube JM, Brahmer JR, Tykodi SS, Easton K, Carvajal RD, Jones PA, Laird PW, Weisenberger DJ, Tsai S, Juergens RA, Topalian SL, Rudin CM, Brock MV, Pardoll D, Baylin SB (2013) Alterations of immune response of non-small cell lung cancer with azacytidine. Oncotarget 4:2067–2079CrossRefPubMedPubMedCentralGoogle Scholar
  83. Xu JZ, Shen J, Cheng YY, Qu HB (2008) Simultaneous detection of seven phenolic acids in Danshen injection using HPLC with ultraviolet detector. J Zhejiang Univ Sci B 9:728–733CrossRefPubMedPubMedCentralGoogle Scholar
  84. Yang X, Wu XZ (2015) Main anti-tumor angiogenesis agents isolated from Chinese herbal medicines. Mini-Rev Med Chem 15:1011–1023CrossRefPubMedGoogle Scholar
  85. Yu DC, Waby JS, Chirakkal H, Staton CA, Corfe BM (2010) Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation. Mol Cancer 9:276CrossRefPubMedPubMedCentralGoogle Scholar
  86. Zecchin A, Pattarini L, Gutierrez MI, Mano M, Mai A, Valente S, Myers MP, Pantano S, Giacca M (2014) Reversible acetylation regulates vascular endothelial growth factor receptor-2 activity. J Mol Cell Biol 6:116–127CrossRefPubMedGoogle Scholar
  87. Zhao Y, Yu D, Wu H, Liu H, Zhou H, Gu R, Zhang R, Zhang S, Wu G (2014) Anticancer activity of SAHA, a potent histone deacetylase inhibitor, in NCI-H460 human large-cell lung carcinoma cells in vitro and in vivo. Int J Oncol 44:451–458CrossRefPubMedGoogle Scholar
  88. Zhao W, Wang Y, Gao N, Han Z, Yu H (2015) Potential anti-cancer effect of curcumin in human lung squamous cell carcinoma. Thorac Cancer 6:508–516CrossRefPubMedPubMedCentralGoogle Scholar
  89. Zheng H, Zhao W, Yan C, Watson CC, Massengill M, Xie M, Massengill C, Noyes DR, Martinez GV, Afzal R, Chen Z, Ren X, Antonia SJ, Haura EB, Ruffell B, Beg AA (2016) HDAC inhibitors enhance T-cell chemokine expression and augment response to PD-1 immunotherapy in lung adenocarcinoma. Clin Cancer Res 22:4119–4132CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Thoracic Oncology Research GroupTrinity Translational Medical Institute, St James’s HospitalDublinIreland

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