Tumor Biology

, Volume 37, Issue 11, pp 14341–14354 | Cite as

Role of angiogenic factors of herbal origin in regulation of molecular pathways that control tumor angiogenesis

  • Manoj Kumar
  • Sunil Kumar Dhatwalia
  • D. K. DhawanEmail author


The formation of blood capillaries to sustain development and growth of new tissues is referred to as angiogenesis. Angiogenesis is pivotal in both carcinogenesis and metastasis since capillaries are the sole source of supplying nutrients and oxygen to the proliferating tumor cells; therefore, this dependency of tumor growth on angiogenesis challenges researchers to halt tumor growth by targeting angiogenesis with the help of either synthetic or natural inhibitors. Many synthetic inhibitors of angiogenesis have not only come into force but also resulted in some severe adverse effects. Natural compounds may effectively fit into this condition and possibly decrease the time of treatment. In the recent past, literature is replete with evidences advocating the usefulness of natural compounds that target multiple biochemical pathways. The additional advantage of natural compounds is that their active principles interact with one another and work synergistically to give more meaningful and reliable effects than individual principle. Hence, if we are somehow able to combine more than two natural compounds, then it may be possible to enhance their potential by many folds, which shall prove to be very effective in combating tumor angiogenesis. This review shall discuss the concept of angiogenesis, molecular pathways, and angiogenic inhibitors and their specific targets and potential of natural compounds to greatly enhance the current knowledge of angiogenesis-inhibiting factors.


Angiogenesis Tumor Natural compounds Signaling molecules 



Authors are thankful to University Grant Commision (UGC), New Delhi, India for providing financial assistance in the form of Dr. DSK Postdoctoral fellowship scheme.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.


  1. 1.
    Polverini PJ. Angiogenesis in health and disease: insights into basic mechanisms and therapeutic opportunities. J Dent Educ. 2002;66:962–75.PubMedGoogle Scholar
  2. 2.
    Ribatti D, Djonov V. Intussusceptive microvascular growth in tumors. Cancer Lett. 2012;316:126–31.PubMedCrossRefGoogle Scholar
  3. 3.
    Bisht M, Dhasmana DC, Bist SS. Angiogenesis: future of pharmacological modulation. Indian J Pharmacol. 2010;42:2–8.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov. 2007;6:273–86.PubMedCrossRefGoogle Scholar
  5. 5.
    Carmeliet P. Angiogenesis in health and disease. Nat Med. 2003;9:653–60.PubMedCrossRefGoogle Scholar
  6. 6.
    Ali TK, El-Remessy AB. Diabetic retinopathy: current management and experimental therapeutic targets. Pharmacotherapy. 2009;29:182–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Willis LM, El-Remessy AB, Somanath PR, Deremer DL, Fagan SC. Angiotensin receptor blockers and angiogenesis: clinical and experimental evidence. Clin Sci (Lond). 2011;120:307–19.CrossRefGoogle Scholar
  8. 8.
    Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 2006;295:2516–24.PubMedCrossRefGoogle Scholar
  9. 9.
    Wang Z, Dabrosin C, Yin X, Fuster MM, Arreola A, Rathmell WK, et al. Broad targeting of angiogenesis for cancer prevention and therapy. Semin Cancer Biol. 2015;35(Suppl):S224–43.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Fayette J, Soria JC, Armand JP. Use of angiogenesis inhibitors in tumour treatment. Eur J Cancer. 2005;41:1109–16.PubMedCrossRefGoogle Scholar
  11. 11.
    Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.PubMedCrossRefGoogle Scholar
  12. 12.
    Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov. 2006;5:835–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Eberhard A, Kahlert S, Goede V, Hemmerlein B, Plate KH, Augustin HG. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res. 2000;60:1388–93.PubMedGoogle Scholar
  14. 14.
    Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest. 1999;103:159–65.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Malhotra A, Nair P, Dhawan DK. Study to evaluate molecular mechanics behind synergistic chemo-preventive effects of curcumin and resveratrol during lung carcinogenesis. PLoS One. 2014;9:e93820.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Aggarwal BB, Prasad S, Reuter S, Kannappan R, Yadev VR, Park B, et al. Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases: “reverse pharmacology” and “bedside to bench” approach. Curr Drug Targets. 2011;12:1595–653.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Papetti M, Herman IM. Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol. 2002;282:C947–70.PubMedCrossRefGoogle Scholar
  18. 18.
    Norrby K. Angiogenesis: new aspects relating to its initiation and control. APMIS. 1997;105:417–37.PubMedCrossRefGoogle Scholar
  19. 19.
    Pandya NM, Dhalla NS, Santani DD. Angiogenesis—a new target for future therapy. Vasc Pharmacol. 2006;44:265–74.CrossRefGoogle Scholar
  20. 20.
    Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis. 2000;21:505–15.PubMedCrossRefGoogle Scholar
  21. 21.
    Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86:353–64.PubMedCrossRefGoogle Scholar
  22. 22.
    Baeriswyl V, Christofori G. The angiogenic switch in carcinogenesis. Semin Cancer Biol. 2009;19:329–37.PubMedCrossRefGoogle Scholar
  23. 23.
    Pepper MS. Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol. 2001;21:1104–17.PubMedCrossRefGoogle Scholar
  24. 24.
    Folkman J, Shing Y. Angiogenesis. J Biol Chem. 1992;267:10931–4.PubMedGoogle Scholar
  25. 25.
    Denekamp J. Review article: angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. Br J Radiol. 1993;66:181–96.PubMedCrossRefGoogle Scholar
  26. 26.
    Adachi S, Nagao T, To S, Joe AK, Shimizu M, Matsushima-Nishiwaki R, et al. (−)-Epigallocatechin gallate causes internalization of the epidermal growth factor receptor in human colon cancer cells. Carcinogenesis. 2008;29:1986–93.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Losordo DW, Dimmeler S. Therapeutic angiogenesis and vasculogenesis for ischemic disease. Part I: angiogenic cytokines. Circulation. 2004;109:2487–91.PubMedCrossRefGoogle Scholar
  28. 28.
    Gasparini G, Longo R, Fanelli M, Teicher BA. Combination of antiangiogenic therapy with other anticancer therapies: results, challenges, and open questions. J Clin Oncol. 2005;23:1295–311.PubMedCrossRefGoogle Scholar
  29. 29.
    Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989;246:1306–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Kolch W, Martiny-Baron G, Kieser A, Marme D. Regulation of the expression of the VEGF/VPS and its receptors: role in tumor angiogenesis. Breast Cancer Res Treat. 1995;36:139–55.PubMedCrossRefGoogle Scholar
  31. 31.
    Sunderkotter C, Steinbrink K, Goebeler M, Bhardwaj R, Sorg C. Macrophages and angiogenesis. J Leukoc Biol. 1994;55:410–22.PubMedGoogle Scholar
  32. 32.
    Motro B, Itin A, Sachs L, Keshet E. Pattern of interleukin 6 gene expression in vivo suggests a role for this cytokine in angiogenesis. Proc Natl Acad Sci U S A. 1990;87:3092–6.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Van Meir EG. Cytokines and tumors of the central nervous system. Glia. 1995;15:264–88.PubMedCrossRefGoogle Scholar
  34. 34.
    Zhang L, Rui YC, Yang PY, Qiu Y, Li TJ, Liu HC. Inhibitory effects of Ginkgo biloba extract on vascular endothelial growth factor in rat aortic endothelial cells. Acta Pharmacol Sin. 2002;23:919–23.PubMedGoogle Scholar
  35. 35.
    Hou Z, Sang S, You H, Lee MJ, Hong J, Chin KV, et al. Mechanism of action of (−)-epigallocatechin-3-gallate: auto-oxidation-dependent inactivation of epidermal growth factor receptor and direct effects on growth inhibition in human esophageal cancer KYSE 150 cells. Cancer Res. 2005;65:8049–56.PubMedCrossRefGoogle Scholar
  36. 36.
    Fajardo LF, Kwan HH, Kowalski J, Prionas SD, Allison AC. Dual role of tumor necrosis factor-alpha in angiogenesis. Am J Pathol. 1992;140:539–44.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Jendraschak E, Sage EH. Regulation of angiogenesis by SPARC and angiostatin: implications for tumor cell biology. Semin Cancer Biol. 1996;7:139–46.PubMedCrossRefGoogle Scholar
  38. 38.
    Gately S, Li WW. Multiple roles of COX-2 in tumor angiogenesis: a target for antiangiogenic therapy. Semin Oncol. 2004;31:2–11.PubMedCrossRefGoogle Scholar
  39. 39.
    Nie D, Krishnamoorthy S, Jin R, Tang K, Chen Y, Qiao Y, et al. Mechanisms regulating tumor angiogenesis by 12-lipoxygenase in prostate cancer cells. J Biol Chem. 2006;281:18601–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Ma ZS, Huynh TH, Ng CP, Do PT, Nguyen TH, Huynh H. Reduction of CWR22 prostate tumor xenograft growth by combined tamoxifen-quercetin treatment is associated with inhibition of angiogenesis and cellular proliferation. Int J Oncol. 2004;24:1297–304.PubMedGoogle Scholar
  41. 41.
    Yadav L, Puri N, Rastogi V, Satpute P, Sharma V. Tumour angiogenesis and angiogenic inhibitors: a review. J Clin Diagn Res. 2015;9:XE01–XE5.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999;13:9–22.PubMedGoogle Scholar
  43. 43.
    Gupta MK, Qin RY. Mechanism and its regulation of tumor-induced angiogenesis. World J Gastroenterol. 2003;9:1144–55.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Huang YH, Yang HY, Hsu YF, Chiu PT, Ou G, Hsu MJ. Src contributes to IL6-induced vascular endothelial growth factor-C expression in lymphatic endothelial cells. Angiogenesis. 2014;17:407–18.PubMedCrossRefGoogle Scholar
  45. 45.
    Nagasaki T, Hara M, Nakanishi H, Takahashi H, Sato M, Takeyama H. Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour-stroma interaction. Br J Cancer. 2014;110:469–78.PubMedCrossRefGoogle Scholar
  46. 46.
    Shao J, Sheng GG, Mifflin RC, Powell DW, Sheng H. Roles of myofibroblasts in prostaglandin E2-stimulated intestinal epithelial proliferation and angiogenesis. Cancer Res. 2006;66:846–55.PubMedCrossRefGoogle Scholar
  47. 47.
    Fagiani E, Lorentz P, Kopfstein L, Christofori G. Angiopoietin-1 and -2 exert antagonistic functions in tumor angiogenesis, yet both induce lymphangiogenesis. Cancer Res. 2011;71:5717–27.PubMedCrossRefGoogle Scholar
  48. 48.
    Harris RE, Casto BC, Harris ZM. Cyclooxygenase-2 and the inflammogenesis of breast cancer. World J Clin Oncol. 2014;5:677–92.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Vosooghi M, Amini M. The discovery and development of cyclooxygenase-2 inhibitors as potential anticancer therapies. Expert Opin Drug Discov. 2014;9:255–67.PubMedCrossRefGoogle Scholar
  50. 50.
    Knab LM, Grippo PJ, Bentrem DJ. Involvement of eicosanoids in the pathogenesis of pancreatic cancer: the roles of cyclooxygenase-2 and 5-lipoxygenase. World J Gastroenterol. 2014;20:10729–39.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Liu B, Qu L, Yan S. Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer Cell Int. 2015.Google Scholar
  52. 52.
    Pidgeon GP, Lysaght J, Krishnamoorthy S, Reynolds JV, O’Byrne K, Nie D, et al. Lipoxygenase metabolism: roles in tumor progression and survival. Cancer Metastasis Rev. 2007;26:503–24.PubMedCrossRefGoogle Scholar
  53. 53.
    Nassar A, Radhakrishnan A, Cabrero IA, Cotsonis G, Cohen C. COX-2 expression in invasive breast cancer: correlation with prognostic parameters and outcome. Appl Immunohistochem Mol Morphol. 2007;15:255–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Nie D, Nemeth J, Qiao Y, Zacharek A, Li L, Hanna K, et al. Increased metastatic potential in human prostate carcinoma cells by overexpression of arachidonate 12-lipoxygenase. Clin Exp Metastasis. 2003;20:657–63.PubMedCrossRefGoogle Scholar
  55. 55.
    Weng CJ, Chou CP, Ho CT, Yen GC. Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol. Mol Nutr Food Res. 2012;56:1304–14.PubMedCrossRefGoogle Scholar
  56. 56.
    Sethi G, Shanmugam MK, Ramachandran L, Kumar AP, Tergaonkar V. Multifaceted link between cancer and inflammation. Biosci Rep. 2012;32:1–15.PubMedCrossRefGoogle Scholar
  57. 57.
    Vaccaro V, Melisi D, Bria E, Cuppone F, Ciuffreda L, Pino MS, et al. Emerging pathways and future targets for the molecular therapy of pancreatic cancer. Expert Opin Ther Targets. 2011;15:1183–96.PubMedCrossRefGoogle Scholar
  58. 58.
    Batra S, Balamayooran G, Sahoo MK. Nuclear factor-kappaB: a key regulator in health and disease of lungs. Arch Immunol Ther Exp. 2011;59:335–51.CrossRefGoogle Scholar
  59. 59.
    Guttridge DC, Albanese C, Reuther JY, Pestell RG, Baldwin Jr AS. NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol Cell Biol. 1999;19:5785–99.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Huber MA, Azoitei N, Baumann B, Grunert S, Sommer A, Pehamberger H, et al. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest. 2004;114:569–81.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Wilczynska KM, Gopalan SM, Bugno M, Kasza A, Konik BS, Bryan L, et al. A novel mechanism of tissue inhibitor of metalloproteinases-1 activation by interleukin-1 in primary human astrocytes. J Biol Chem. 2006;281:34955–64.PubMedCrossRefGoogle Scholar
  62. 62.
    Liu RM. Oxidative stress, plasminogen activator inhibitor 1, and lung fibrosis. Antioxid Redox Signal. 2008;10:303–19.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Davis ME, Chen ZG, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008;7:771–82.PubMedCrossRefGoogle Scholar
  64. 64.
    Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002;20:4368–80.PubMedCrossRefGoogle Scholar
  65. 65.
    Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF Receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol. 2006;7:359–71.PubMedCrossRefGoogle Scholar
  66. 66.
    Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542–50.PubMedCrossRefGoogle Scholar
  67. 67.
    Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–76.PubMedCrossRefGoogle Scholar
  68. 68.
    Penson RT, Huang HQ, Wenzel LB, Monk BJ, Stockman S, Long 3rd HJ, et al. Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240. Lancet Oncol. 2015;16:301–11.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Niu G, Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Curr Drug Targets. 2010;11:1000–17.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125–34.PubMedCrossRefGoogle Scholar
  71. 71.
    Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRefGoogle Scholar
  72. 72.
    Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM, Lynch M. Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther. 2008;7:3129–40.PubMedCrossRefGoogle Scholar
  73. 73.
    Mesa RA. Tipifarnib: farnesyl transferase inhibition at a crossroads. Expert Rev Anticancer Ther. 2006;6:313–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Liu M, Bryant MS, Chen J, Lee S, Yaremko B, Lipari P, et al. Antitumor activity of SCH 66336, an orally bioavailable tricyclic inhibitor of farnesyl protein transferase, in human tumor xenograft models and wap-ras transgenic mice. Cancer Res. 1998;58:4947–56.PubMedGoogle Scholar
  75. 75.
    Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov. 2006;5:671–88.PubMedCrossRefGoogle Scholar
  76. 76.
    Hurwitz H, Saini S. Bevacizumab in the treatment of metastatic colorectal cancer: safety profile and management of adverse events. Semin Oncol. 2006;33:S26–34.PubMedCrossRefGoogle Scholar
  77. 77.
    Elice F, Rodeghiero F. Bleeding complications of antiangiogenic therapy: pathogenetic mechanisms and clinical impact. Thromb Res. 2010;125(Suppl 2):S55–7.PubMedCrossRefGoogle Scholar
  78. 78.
    Verheul HM, Pinedo HM. Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition. Nat Rev Cancer. 2007;7:475–85.PubMedCrossRefGoogle Scholar
  79. 79.
    Los M, Roodhart JM, Voest EE. Target practice: lessons from phase III trials with bevacizumab and vatalanib in the treatment of advanced colorectal cancer. Oncologist. 2007;12:443–50.PubMedCrossRefGoogle Scholar
  80. 80.
    Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol. 2003;21:60–5.PubMedCrossRefGoogle Scholar
  81. 81.
    Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007;25:1539–44.PubMedCrossRefGoogle Scholar
  82. 82.
    Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004;22:2184–91.PubMedCrossRefGoogle Scholar
  83. 83.
    Kimura Y, Okuda H. Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice. J Nutr. 2001;131:1844–9.PubMedGoogle Scholar
  84. 84.
    Banerjee S, Bueso-Ramos C, Aggarwal BB. Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res. 2002;62:4945–54.PubMedGoogle Scholar
  85. 85.
    Sagar SM, Yance D, Wong RK. Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-part 1. Curr Oncol. 2006;13:14–26.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Fassina G, Vene R, Morini M, Minghelli S, Benelli R, Noonan DM, et al. Mechanisms of inhibition of tumor angiogenesis and vascular tumor growth by epigallocatechin-3-gallate. Clin Cancer Res. 2004;10:4865–73.PubMedCrossRefGoogle Scholar
  87. 87.
    Kondo T, Ohta T, Igura K, Hara Y, Kaji K. Tea catechins inhibit angiogenesis in vitro, measured by human endothelial cell growth, migration and tube formation, through inhibition of VEGF receptor binding. Cancer Lett. 2002;180:139–44.PubMedCrossRefGoogle Scholar
  88. 88.
    Kojima-Yuasa A, Hua JJ, Kennedy DO, Matsui-Yuasa I. Green tea extract inhibits angiogenesis of human umbilical vein endothelial cells through reduction of expression of VEGF receptors. Life Sci. 2003;73:1299–313.PubMedCrossRefGoogle Scholar
  89. 89.
    Lamy S, Gingras D, Beliveau R. Green tea catechins inhibit vascular endothelial growth factor receptor phosphorylation. Cancer Res. 2002;62:381–5.PubMedGoogle Scholar
  90. 90.
    Gu JW, Makey KL, Tucker KB, Chinchar E, Mao X, Pei I, et al. EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1alpha and NFkappaB, and VEGF expression. Vasc Cell. 2013;5:9.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Zhou HJ, Wang WQ, Wu GD, Lee J, Li A. Artesunate inhibits angiogenesis and downregulates vascular endothelial growth factor expression in chronic myeloid leukemia K562 cells. Vasc Pharmacol. 2007;47:131–8.CrossRefGoogle Scholar
  92. 92.
    Rodriguez SK, Guo W, Liu L, Band MA, Paulson EK, Meydani M. Green tea catechin, epigallocatechin-3-gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex. Int J Cancer. 2006;118:1635–44.PubMedCrossRefGoogle Scholar
  93. 93.
    Liang YC, Lin-shiau SY, Chen CF, Lin JK. Suppression of extracellular signals and cell proliferation through EGF receptor binding by (−)-epigallocatechin gallate in human A431 epidermoid carcinoma cells. J Cell Biochem. 1997;67:55–65.PubMedCrossRefGoogle Scholar
  94. 94.
    Adachi S, Nagao T, Ingolfsson HI, Maxfield FR, Andersen OS, Kopelovich L, et al. The inhibitory effect of (−)-epigallocatechin gallate on activation of the epidermal growth factor receptor is associated with altered lipid order in HT29 colon cancer cells. Cancer Res. 2007;67:6493–501.PubMedCrossRefGoogle Scholar
  95. 95.
    Arbiser JL, Klauber N, Rohan R, van Leeuwen R, Huang MT, Fisher C, et al. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med. 1998;4:376–83.PubMedPubMedCentralGoogle Scholar
  96. 96.
    Mohan R, Sivak J, Ashton P, Russo LA, Pham BQ, Kasahara N, et al. Curcuminoids inhibit the angiogenic response stimulated by fibroblast growth factor-2, including expression of matrix metalloproteinase gelatinase B. J Biol Chem. 2000;275:10405–12.PubMedCrossRefGoogle Scholar
  97. 97.
    Binion DG, Otterson MF, Rafiee P. Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition. Gut. 2008;57:1509–17.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Shan B, Schaaf C, Schmidt A, Lucia K, Buchfelder M, Losa M, et al. Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas. J Endocrinol. 2012;214:389–98.PubMedCrossRefGoogle Scholar
  99. 99.
    Bae MK, Kim SH, Jeong JW, Lee YM, Kim HS, Kim SR, et al. Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1. Oncol Rep. 2006;15:1557–62.PubMedGoogle Scholar
  100. 100.
    Gururaj AE, Belakavadi M, Venkatesh DA, Marme D, Salimath BP. Molecular mechanisms of anti-angiogenic effect of curcumin. Biochem Biophys Res Commun. 2002;297:934–42.PubMedCrossRefGoogle Scholar
  101. 101.
    El-Azab M, Hishe H, Moustafa Y, El-Awadyel S. Anti-angiogenic effect of resveratrol or curcumin in Ehrlich ascites carcinoma-bearing mice. Eur J Pharmacol. 2011;652:7–14.PubMedCrossRefGoogle Scholar
  102. 102.
    Hahm ER, Gho YS, Park S, Park C, Kim KW, Yang CH. Synthetic curcumin analogs inhibit activator protein-1 transcription and tumor-induced angiogenesis. Biochem Biophys Res Commun. 2004;321:337–44.PubMedCrossRefGoogle Scholar
  103. 103.
    Chen HW, Yu SL, Chen JJ, Li HN, Lin YC, Yao PL, et al. Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis. Mol Pharmacol. 2004;65:99–110.PubMedCrossRefGoogle Scholar
  104. 104.
    Leu TH, Su SL, Chuang YC, Maa MC. Direct inhibitory effect of curcumin on Src and focal adhesion kinase activity. Biochem Pharmacol. 2003;66:2323–31.PubMedCrossRefGoogle Scholar
  105. 105.
    Sugiyama S, Yoshino Y, Kuriyama S, Inoue M, Komine K, Otsuka K, et al. A curcumin analog, GO-Y078, effectively inhibits angiogenesis through actin disorganization. Anti Cancer Agents Med Chem. 2016;16:633–47.CrossRefGoogle Scholar
  106. 106.
    Huang YF, Zhu XX, Ding ZS, Lv GY. Study on anti-angiogenesis effect of three curcumin pigments and expression of their relevant factors. Zhongguo Zhong Yao Za Zhi. 2015;40:324–9.PubMedGoogle Scholar
  107. 107.
    Zhang F, Zhang Z, Chen L, Kong D, Zhang X, Lu C, et al. Curcumin attenuates angiogenesis in liver fibrosis and inhibits angiogenic properties of hepatic stellate cells. J Cell Mol Med. 2014;18:1392–406.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Cao Z, Fang J, Xia C, Shi X, Jiang BH. Trans-3,4,5′-Trihydroxystibene inhibits hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression in human ovarian cancer cells. Clin Cancer Res. 2004;10:5253–63.PubMedCrossRefGoogle Scholar
  109. 109.
    Zhang H, Yang R. Resveratrol inhibits VEGF gene expression and proliferation of hepatocarcinoma cells. Hepato-Gastroenterology. 2014;61:410–2.PubMedGoogle Scholar
  110. 110.
    Kim DH, Hossain MA, Kim MY, Kim JA, Yoon JH, Suh HS, et al. A novel resveratrol analogue, HS-1793, inhibits hypoxia-induced HIF-1alpha and VEGF expression, and migration in human prostate cancer cells. Int J Oncol. 2013;43:1915–24.PubMedGoogle Scholar
  111. 111.
    Kimura Y, Sumiyoshi M, Baba K. Antitumor activities of synthetic and natural stilbenes through antiangiogenic action. Cancer Sci. 2008;99:2083–96.PubMedCrossRefGoogle Scholar
  112. 112.
    Srivastava RK, Unterman TG, Shankar SFOXO. Transcription factors and VEGF neutralizing antibody enhance antiangiogenic effects of resveratrol. Mol Cell Biochem. 2010;337:201–12.PubMedCrossRefGoogle Scholar
  113. 113.
    Aldieri E, Atragene D, Bergandi L, Riganti C, Costamagna C, Bosia A, et al. Artemisinin inhibits inducible nitric oxide synthase and nuclear factor NF-κB activation. FEBS Lett. 2003;552:141–4.PubMedCrossRefGoogle Scholar
  114. 114.
    Harvey Lodish A B, S Lawrence Zipursky, Paul Matsudaira, David Baltimore, James Darnell., Molecular Cell Biology. 5 ed, ed. H. Lodish. 2003: Freeman, W. H. & Company. 973.Google Scholar
  115. 115.
    Liu JJ, Huang TS, Cheng WF, Lu FJ. Baicalein and baicalin are potent inhibitors of angiogenesis: inhibition of endothelial cell proliferation, migration and differentiation. Int J Cancer. 2003;106:559–65.PubMedCrossRefGoogle Scholar
  116. 116.
    Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009;9:429–39.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Jung YD, Kim MS, Shin BA, Chay KO, Ahn BW, Liu W, et al. EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. Br J Cancer. 2001;84:844–50.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Lee MJ, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, et al. Pharmacokinetics of tea catechins after ingestion of green tea and (−)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomark Prev. 2002;11:1025–32.Google Scholar
  119. 119.
    Sartippour MR, Shao ZM, Heber D, Beatty P, Zhang L, Liu C, et al. Green tea inhibits vascular endothelial growth factor (VEGF) induction in human breast cancer cells. J Nutr. 2002;132:2307–11.PubMedGoogle Scholar
  120. 120.
    Zhu BH, Zhan WH, Li ZR, Wang Z, He YL, Peng JS, et al. (−)-Epigallocatechin-3-gallate inhibits growth of gastric cancer by reducing VEGF production and angiogenesis. World J Gastroenterol. 2007;13:1162–9.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Cao Y, Cao R. Angiogenesis inhibited by drinking tea. Nature. 1999;398:381.PubMedCrossRefGoogle Scholar
  122. 122.
    Peschard P, Park M. From Tpr-Met to Met, tumorigenesis and tubes. Oncogene. 2007;26:1276–85.PubMedCrossRefGoogle Scholar
  123. 123.
    Shanafelt TD, Call TG, Zent CS, LaPlant B, Bowen DA, Roos M, et al. Phase I trial of daily oral polyphenon E in patients with asymptomatic Rai stage 0 to II chronic lymphocytic leukemia. J Clin Oncol. 2009;27:3808–14.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Shanafelt TD, Call TG, Zent CS, Leis JF, LaPlant B, Bowen DA, et al. Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia. Cancer. 2013;119:363–70.PubMedCrossRefGoogle Scholar
  125. 125.
    Zhao H, Zhu W, Xie P, Li H, Zhang X, Sun X, et al. A phase I study of concurrent chemotherapy and thoracic radiotherapy with oral epigallocatechin-3-gallate protection in patients with locally advanced stage III non-small-cell lung cancer. Radiother Oncol. 2014;110:132–6.PubMedCrossRefGoogle Scholar
  126. 126.
    Zhao H, Zhu W, Jia L, Sun X, Chen G, Zhao X, et al. Phase I study of topical epigallocatechin-3-gallate (EGCG) in patients with breast cancer receiving adjuvant radiotherapy. Br J Radiol. 2016;89:20150665.PubMedCrossRefGoogle Scholar
  127. 127.
    Narayan S. Curcumin, a multi-functional chemopreventive agent, blocks growth of colon cancer cells by targeting beta-catenin-mediated transactivation and cell-cell adhesion pathways. J Mol Histol. 2004;35:301–7.PubMedCrossRefGoogle Scholar
  128. 128.
    Nair P, Malhotra A, Dhawan DK. Curcumin and quercetin trigger apoptosis during benzo(a)pyrene-induced lung carcinogenesis. Mol Cell Biochem. 2015;400:51–6.PubMedCrossRefGoogle Scholar
  129. 129.
    Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003;23:363–98.PubMedGoogle Scholar
  130. 130.
    Kelloff GJ, Crowell JA, Hawk ET, Steele VE, Lubet RA, Boone CW, et al. Strategy and planning for chemopreventive drug development: clinical development plans II. J Cell Biochem Suppl. 1996;26:54–71.PubMedCrossRefGoogle Scholar
  131. 131.
    Jain K, Dhawan DK. Regulation of biokinetics of (65)Zn by curcumin and zinc in experimentally induced colon carcinogenesis in rats. Cancer Biother Radiopharm. 2014;29:310–6.PubMedCrossRefGoogle Scholar
  132. 132.
    Bhandarkar SS, Arbiser JL. Curcumin as an inhibitor of angiogenesis. Adv Exp Med Biol. 2007;595:185–95.PubMedCrossRefGoogle Scholar
  133. 133.
    Mohankumar K, Sridharan S, Pajaniradje S, Singh VK, Ronsard L, Banerjea AC, et al. BDMC-A, an analog of curcumin, inhibits markers of invasion, angiogenesis, and metastasis in breast cancer cells via NF-kappaB pathway--a comparative study with curcumin. Biomed Pharmacother. 2015;74:178–86.PubMedCrossRefGoogle Scholar
  134. 134.
    James MI, Iwuji C, Irving G, Karmokar A, Higgins JA, Griffin-Teal N, et al. Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett. 2015;364:135–41.PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Carroll RE, Benya RV, Turgeon DK, Vareed S, Neuman M, Rodriguez L, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila). 2011;4:354–64.CrossRefGoogle Scholar
  136. 136.
    Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, 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.PubMedGoogle Scholar
  137. 137.
    Dhillon N, Aggarwal BB, Newman RA, Wolff RA, Kunnumakkara AB, Abbruzzese JL, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. 2008;14:4491–9.PubMedCrossRefGoogle Scholar
  138. 138.
    Golombick T, Diamond TH, Badmaev V, Manoharan A, Ramakrishna R. The potential role of curcumin in patients with monoclonal gammopathy of undefined significance—its effect on paraproteinemia and the urinary N-telopeptide of type I collagen bone turnover marker. Clin Cancer Res. 2009;15:5917–22.PubMedCrossRefGoogle Scholar
  139. 139.
    Panahi Y, Saadat A, Beiraghdar F, Sahebkar A. Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial. Phytother Res. 2014;28:1461–7.PubMedCrossRefGoogle Scholar
  140. 140.
    Ryan JL, Heckler CE, Ling M, Katz A, Williams JP, Pentland AP, et al. Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res. 2013;180:34–43.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Irving GR, Iwuji CO, Morgan B, Berry DP, Steward WP, Thomas A, et al. Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer (CUFOX): study protocol for a randomised control trial. Trials. 2015;16:110.PubMedPubMedCentralCrossRefGoogle Scholar
  142. 142.
    Huang SS, Tsai MC, Chih CL, Hung LM, Tsai SK. Resveratrol reduction of infarct size in Long-Evans rats subjected to focal cerebral ischemia. Life Sci. 2001;69:1057–65.PubMedCrossRefGoogle Scholar
  143. 143.
    Sebastia N, Montoro A, Manes J, Soriano JM. A preliminary study of presence of resveratrol in skins and pulps of European and Japanese plum cultivars. J Sci Food Agric. 2012;92:3091–4.PubMedCrossRefGoogle Scholar
  144. 144.
    Sun AY, Wang Q, Simonyi A, Sun GY. Resveratrol as a therapeutic agent for neurodegenerative diseases. Mol Neurobiol. 2010;41:375–83.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Sonnett TE, Levien TL, Gates BJ, Robinson JD, Campbell RK. Diabetes mellitus, inflammation, obesity: proposed treatment pathways for current and future therapies. Ann Pharmacother. 2010;44:701–11.PubMedCrossRefGoogle Scholar
  146. 146.
    Speakman JR, Mitchell SE. Caloric restriction. Mol Asp Med. 2011;32:159–221.CrossRefGoogle Scholar
  147. 147.
    Malhotra A, Nair P, Dhawan DK. Modulatory effects of curcumin and resveratrol on lung carcinogenesis in mice. Phytother Res. 2010;24:1271–7.PubMedCrossRefGoogle Scholar
  148. 148.
    Malhotra A, Nair P, Dhawan DK. Curcumin and resveratrol in combination modulates benzo(a)pyrene-induced genotoxicity during lung carcinogenesis. Hum Exp Toxicol. 2012;31:1199–206.PubMedCrossRefGoogle Scholar
  149. 149.
    Borriello A, Bencivenga D, Caldarelli I, Tramontano A, Borgia A, Zappia V, et al. Resveratrol: from basic studies to bedside. Cancer Treat Res. 2014;159:167–84.PubMedCrossRefGoogle Scholar
  150. 150.
    Brakenhielm E, Cao R, Cao Y. Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes. FASEB J. 2001;15:1798–800.PubMedGoogle Scholar
  151. 151.
    Howells LM, Berry DP, Elliott PJ, Jacobson EW, Hoffmann E, Hegarty B, et al. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases—safety, pharmacokinetics, and pharmacodynamics. Cancer Prev Res (Phila). 2011;4:1419–25.CrossRefGoogle Scholar
  152. 152.
    Ji Q, Liu X, Fu X, Zhang L, Sui H, Zhou L, et al. Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/beta-catenin signal pathway. PLoS One. 2013;8:e78700.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Zhu W, Qin W, Zhang K, Rottinghaus GE, Chen YC, Kliethermes B, et al. Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer. Nutr Cancer. 2012;64:393–400.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Mueller MS, Runyambo N, Wagner I, Borrmann S, Dietz K, Heide L. Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria. Trans R Soc Trop Med Hyg. 2004;98:318–21.PubMedCrossRefGoogle Scholar
  155. 155.
    Singh NP, Lai HC. Artemisinin induces apoptosis in human cancer cells. Anticancer Res. 2004;24:2277–80.PubMedGoogle Scholar
  156. 156.
    Anfosso L, Efferth T, Albini A, Pfeffer U. Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins. Pharmacogenomics J. 2006;6:269–78.PubMedGoogle Scholar
  157. 157.
    Konig M, von Hagens C, Hoth S, Baumann I, Walter-Sack I, Edler L, et al. Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, uncontrolled, monocentric phase I study. Cancer Chemother Pharmacol. 2016;77:413–27.PubMedCrossRefGoogle Scholar
  158. 158.
    Zhang ZY, Yu SQ, Miao LY, Huang XY, Zhang XP, Zhu YP, et al. Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: a randomized controlled trial. Zhong Xi Yi Jie He Xue Bao. 2008;6:134–8.PubMedCrossRefGoogle Scholar
  159. 159.
    Jansen FH, Adoubi IJCK, DE Cnodder T, Jansen N, Tschulakow A, et al. First study of oral Artenimol-R in advanced cervical cancer: clinical benefit, tolerability and tumor markers. Anticancer Res. 2011;31:4417–22.PubMedGoogle Scholar
  160. 160.
    Saraswati S, Pandey M, Mathur R, Agrawal SS. Boswellic acid inhibits inflammatory angiogenesis in a murine sponge model. Microvasc Res. 2011;82:263–8.PubMedCrossRefGoogle Scholar
  161. 161.
    Takada Y, Ichikawa H, Badmaev V, Aggarwal BB. Acetyl-11-keto-beta-boswellic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing NF-kappa B and NF-kappa B-regulated gene expression. J Immunol. 2006;176:3127–40.PubMedCrossRefGoogle Scholar
  162. 162.
    Catanzaro D, Rancan S, Orso G, Dall’Acqua S, Brun P, Giron MC, et al. Boswellia serrata preserves intestinal epithelial barrier from oxidative and inflammatory damage. PLoS One. 2015;10:e0125375.PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Pang X, Yi Z, Zhang X, Sung B, Qu W, Lian X, et al. Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. Cancer Res. 2009;69:5893–900.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Kunnumakkara AB, Nair AS, Sung B, Pandey MK, Aggarwal BB. Boswellic acid blocks signal transducers and activators of transcription 3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase SHP-1. Mol Cancer Res. 2009;7:118–28.PubMedPubMedCentralCrossRefGoogle Scholar
  165. 165.
    Lulli M, Cammalleri M, Fornaciari I, Casini G, Dal Monte M. Acetyl-11-keto-beta-boswellic acid reduces retinal angiogenesis in a mouse model of oxygen-induced retinopathy. Exp Eye Res. 2015;135:67–80.PubMedCrossRefGoogle Scholar
  166. 166.
    Kirste S, Treier M, Wehrle SJ, Becker G, Abdel-Tawab M, Gerbeth K, et al. Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: a prospective, randomized, placebo-controlled, double-blind pilot trial. Cancer. 2011;117:3788–95.PubMedCrossRefGoogle Scholar
  167. 167.
    Calzavara-Pinton P, Zane C, Facchinetti E, Capezzera R, Pedretti A. Topical boswellic acids for treatment of photoaged skin. Dermatol Ther. 2010;23(Suppl 1):S28–32.PubMedCrossRefGoogle Scholar
  168. 168.
    Togni S, Maramaldi G, Bonetta A, Giacomelli L, Di Pierro F. Clinical evaluation of safety and efficacy of Boswellia-based cream for prevention of adjuvant radiotherapy skin damage in mammary carcinoma: a randomized placebo controlled trial. Eur Rev Med Pharmacol Sci. 2015;19:1338–44.PubMedGoogle Scholar
  169. 169.
    Trompezinski S, Bonneville M, Pernet I, Denis A, Schmitt D, Viac J. Gingko biloba extract reduces VEGF and CXCL-8/IL-8 levels in keratinocytes with cumulative effect with epigallocatechin-3-gallate. Arch Dermatol Res. 2010;302:183–9.PubMedCrossRefGoogle Scholar
  170. 170.
    Sun BL, Hu DM, Yuan H, Ye WJ, Wang XC, Xia ZL, et al. Extract of Ginkgo biloba promotes the expression of VEGF following subarachnoid hemorrhage in rats. Int J Neurosci. 2009;119:995–1005.PubMedCrossRefGoogle Scholar
  171. 171.
    Koltermann A, Liebl J, Furst R, Ammer H, Vollmar AM, Zahler S. Ginkgo biloba Extract EGb 761 exerts anti-angiogenic effects via activation of tyrosine phosphatases. J Cell Mol Med. 2009;13:2122–30.PubMedCrossRefGoogle Scholar
  172. 172.
    Tilley C, Deep G, Agarwal C, Wempe MF, Biedermann D, Valentova K, et al. Silibinin and its 2,3-dehydro-derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation. Mol Carcinog. 2016;55:3–14.PubMedCrossRefGoogle Scholar
  173. 173.
    Kim S, Jeon M, Lee J, Han J, Oh SJ, Jung T, et al. Induction of fibronectin in response to epidermal growth factor is suppressed by silibinin through the inhibition of STAT3 in triple negative breast cancer cells. Oncol Rep. 2014;32:2230–6.PubMedGoogle Scholar
  174. 174.
    Kil WH, Kim SM, Lee JE, Park KS, Nam SJ. Anticancer effect of silibinin on the xenograft model using MDA-MB-468 breast cancer cells. Ann Surg Treat Res. 2014;87:167–73.PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Harmsma M, Gromme M, Ummelen M, Dignef W, Tusenius KJ, Ramaekers FC. Differential effects of Viscum album extract IscadorQu on cell cycle progression and apoptosis in cancer cells. Int J Oncol. 2004;25:1521–9.PubMedGoogle Scholar
  176. 176.
    Park WB, Lyu SY, Kim JH, Choi SH, Chung HK, Ahn SH, et al. Inhibition of tumor growth and metastasis by Korean mistletoe lectin is associated with apoptosis and antiangiogenesis. Cancer Biother Radiopharm. 2001;16:439–47.PubMedCrossRefGoogle Scholar
  177. 177.
    Miocinovic R, McCabe NP, Keck RW, Jankun J, Hampton JA, Selman SH. In vivo and in vitro effect of baicalein on human prostate cancer cells. Int J Oncol. 2005;26:241–6.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Manoj Kumar
    • 1
  • Sunil Kumar Dhatwalia
    • 1
  • D. K. Dhawan
    • 1
    Email author
  1. 1.Departments of BiophysicsPanjab UniversityChandigarhIndia

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