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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Natural Sourced Inhibitors of EGFR, PDGFR, FGFR and VEGFRMediated Signaling Pathways as Potential Anticancer Agents

Author(s): Sisir Nandi*, Rishita Dey, Asmita Samadder, Aaruni Saxena and Anil Kumar Saxena*

Volume 29, Issue 2, 2022

Published on: 03 March, 2021

Page: [212 - 234] Pages: 23

DOI: 10.2174/0929867328666210303101345

Price: $65


The molecular mechanisms of mitotic cell cycle progression involve very tightly restricted types of machinery which are highly regulated by a fine balance between the positive and negative accelerators (or regulators). These regulators include several checkpoints that have proteins acting as enzymes and their activating partners. These checkpoints incessantly monitor the external as well as internal environments such as growth signals, favorable conditions for growth, cell size, DNA integrity of the cell and hence function to maintain the highly ordered cell cycle progression by sustaining cell homeostasis and promoting error-free DNA replication and cell cycle division. To progress through the mitotic cell cycle, the cell has to successfully drive past the cell cycle checkpoints. Due to the abnormal behavior of some cell cycle proteins, the cells tend to divide continuously overcoming the tight regulation of cell cycle checkpoints. Such anomalies may lead to unwanted cell division, and this deregulation of cell cycle events is considered as one of the main reasons behind tumor development, and thus, cancer progression. So the understanding of the molecular mechanisms in cancer progression might be insightful for designing several cancer treatment strategies. The deregulation in the checkpoints is caused due to the changes in the tyrosine residues of TPKs via PDGFR, EGFR, FGFR, and VEGFR-mediated signaling pathways. Therefore, the inhibitors of PDGFR, EGFR, FGFR, and VEGFR-mediated signaling pathways could be potential anticancer agents. The resistance and toxicity in the existing synthetic anticancer chemotherapeutics may decrease the life span of a patient. For long, natural products have played an essential alternative source of therapeutic agents due to having least or no side effect and toxicity. The present study is an attempt to promote natural anticancer drug development focusing on the updated structural information of PDGFR, EGFR, FGFR, and VEGFR inhibitors isolated from the plant sources. The data used in this review has been collected from internet resources, viz. GOOGLE Web, GOOGLE SCHOLAR, and PubMed Central. The citation of each report was first checked, after which the articles were selected as an authentic reference for the present study. Around 200 journal articles were initially selected, of which around 142 were finally chosen for presenting the study on the natural sourced inhibitors of EGFR, PDGFR, FGFR, and VEGFR-mediated signaling pathways which may help to enhance the potential cancer treatment.

Keywords: Cancer targets, PDGFR, EGFR, FGFR, VEGFR, abnormal signal transduction, natural inhibitors.

W.H.O. Cancer. Available at: accessed at: September 20, 2020.
Waugh, A.; Grant, A. Ross and Wilson Anatomy and physiology in Health and Illness, 3rd ed.; Churchill Livingstone, Elsevier: London, 2006.
Hartwell, L.H.; Weinert, T.A. Checkpoints: controls that ensure the order of cell cycle events. Science, 1989, 246(4930), 629-634.
[] [PMID: 2683079]
Satyanarayana, U.; Chakrapani, U. Biochemistry, 4th ed.; Elsevier: India, 2013.
Hunter, T.; Pines, J. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell, 1994, 79(4), 573-582.
[] [PMID: 7954824]
Park, M.-T.; Lee, S.-J. Cell cycle and cancer. J. Biochem. Mol. Biol., 2003, 36(1), 60-65.
[] [PMID: 12542976]
Kamb, A. Cell-cycle regulators and cancer. Trends Genet., 1995, 11(4), 136-140.
[] [PMID: 7732591]
Ko, L.J.; Prives, C. p53: puzzle and paradigm. Genes Dev., 1996, 10(9), 1054-1072.
[] [PMID: 8654922]
Vermeulen, K.; Van Bockstaele, D.R.; Berneman, Z.N. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif., 2003, 36(3), 131-149.
[] [PMID: 12814430]
Wölfel, T.; Hauer, M.; Schneider, J.; Serrano, M.; Wölfel, C.; Klehmann-Hieb, E.; De Plaen, E.; Hankeln, T.; Meyer zum Büschenfelde, K.H.; Beach, D. A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science, 1995, 269(5228), 1281-1284.
[] [PMID: 7652577]
Heichman, K.A.; Roberts, J.M. Rules to replicate by. Cell, 1994, 79(4), 557-562.
[] [PMID: 7954822]
Motokura, T.; Bloom, T.; Kim, H.G.; Jüppner, H.; Ruderman, J.V.; Kronenberg, H.M.; Arnold, A. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature, 1991, 350(6318), 512-515.
[] [PMID: 1826542]
Li, Y.; Wei, J.; Xu, C.; Zhao, Z.; You, T. Prognostic significance of cyclin D1 expression in colorectal cancer: a meta-analysis of observational studies. PLoS One, 2014, 9(4), e94508.
[] [PMID: 24728073]
Comstock, C.E.S.; Revelo, M.P.; Buncher, C.R.; Knudsen, K.E. Impact of differential cyclin D1 expression and localisation in prostate cancer. Br. J. Cancer, 2007, 96(6), 970-979.
[] [PMID: 17375037]
Metibemu, D.S.; Akinloye, O.A.; Akamo, A.J.; Ojo, D.A.; Okeowo, O.T.; Omotuyi, I.O. Exploring receptor tyrosine kinases-inhibitors in Cancer treatments. Egypt. J. Med. Hum. Genet., 2019, 20(1)
Porter, A.C.; Vaillancourt, R.R. Tyrosine kinase receptor-activated signal transduction pathways which lead to oncogenesis. Oncogene, 1998, 17(11 Reviews), 1343-1352.
[] [PMID: 9779982]
Manning, G.; Whyte, D.B.; Martinez, R.; Hunter, T.; Sudarsanam, S. The protein kinase complement of the human genome. Science, 2002, 298(5600), 1912-1934.
[] [PMID: 12471243]
Du, Z.; Lovly, C.M. Mechanisms of receptor tyrosine kinase activation in cancer. Mol. Cancer, 2018, 17(1), 58.
[] [PMID: 29455648]
Paul, M.K.; Mukhopadhyay, A.K. Tyrosine kinase – Role and significance in Cancer. Int. J. Res. Med. Sci., 2004, 101-115..
[] [PMID: 15912202]
Abram, C.L.; Courtneidge, S.A. Src family tyrosine kinases and growth factor signaling. Exp. Cell Res., 2000, 254(1), 1-13.
[] [PMID: 10623460]
Thomas, S.J.; Snowden, J.A.; Zeidler, M.P.; Danson, S.J. The role of JAK/STAT signalling in the pathogenesis, prognosis and treatment of solid tumours. Br. J. Cancer, 2015, 113(3), 365-371.
[] [PMID: 26151455]
Butti, R.; Das, S.; Gunasekaran, V.P.; Yadav, A.S.; Kumar, D.; Kundu, G.C. Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges. Mol. Cancer, 2018, 17(1), 34.
[] [PMID: 29455658]
Mahajan, K.; Mahajan, N.P. Cross talk of tyrosine kinases with the DNA damage signaling pathways. Nucleic Acids Res., 2015, 43(22), 10588-10601.
[] [PMID: 26546517]
Herbst, R.S. Review of epidermal growth factor receptor biology. Int. J. Radiat. Oncol. Biol. Phys., 2004, 59(2)(Suppl.), 21-26.
[] [PMID: 15142631]
Harris, R.C.; Chung, E.; Coffey, R.J. EGF receptor ligands. Exp. Cell Res., 2003, 284(1), 2-13.
[] [PMID: 12648462]
Woodburn, J.R. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol. Ther., 1999, 82(2-3), 241-250.
[] [PMID: 10454201]
Fry, D.W. Inhibition of the epidermal growth factor receptor family of tyrosine kinases as an approach to cancer chemotherapy: progression from reversible to irreversible inhibitors. Pharmacol. Ther., 1999, 82(2-3), 207-218.
[] [PMID: 10454198]
Thisse, B.; Thisse, C. Function and regulation of FGF signaling during embryonic development. Dev. Biol., 2005, 287(2), 390-402.
[] [PMID: 16216232]
Turner, N.; Grose, R. Fibroblast growth factor signalling: from development to cancer. Nat. Rev. Cancer, 2010, 10(2), 116-129.
[] [PMID: 20094046]
Dienstmann, R.; Rodon, J.; Prat, A.; Perez-Garcia, J.; Adamo, B.; Felip, E.; Cortes, J.; Iafrate, A.J.; Nuciforo, P.; Tabernero, J. Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors. Ann. Oncol., 2014, 25(3), 552-563.
[] [PMID: 24265351]
Touat, M.; Ileana, E.; Postel-Vinay, S.; André, F.; Soria, J.C. Targeting FGFR Signaling in Cancer. Clin. Cancer Res., 2015, 21(12), 2684-2694.
[] [PMID: 26078430]
Ornitz, D.M.; Itoh, N. Fibroblast growth factors. Genome Biol., 2001, 2(3), S3005.
[] [PMID: 11276432]
Dailey, L.; Ambrosetti, D.; Mansukhani, A.; Basilico, C. Mechanisms underlying differential responses to FGF signaling. Cytokine Growth Factor Rev., 2005, 16(2), 233-247.
[] [PMID: 15863038]
Beenken, A.; Mohammadi, M. The FGF family: biology, pathophysiology and therapy. Nat. Rev. Drug Discov., 2009, 8(3), 235-253.
[] [PMID: 19247306]
Dieci, M.V.; Arnedos, M.; Andre, F.; Soria, J.C. Fibroblast growth factor receptor inhibitors as a cancer treatment: from a biologic rationale to medical perspectives. Cancer Discov., 2013, 3(3), 264-279.
[] [PMID: 23418312]
Dorey, K.; Amaya, E. FGF signalling: diverse roles during early vertebrate embryogenesis. Development, 2010, 137(22), 3731-3742.
[] [PMID: 20978071]
Ross, R.; Raines, E.W.; Bowen-Pope, D.F. The biology of platelet-derived growth factor. Cell, 1986, 46(2), 155-169.
[] [PMID: 3013421]
Hannink, M.; Donoghue, D.J. Structure and function of platelet-derived growth factor (PDGF) and related proteins. Biochim. Biophys. Acta, 1989, 989(1), 1-10.
[] [PMID: 2546599]
Heldin, C-H.; Westermark, B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol. Rev., 1999, 79(4), 1283-1316.
[] [PMID: 10508235]
Heldin, C-H.; Lennartsson, J. Structural and functional properties of platelet-derived growth factor and stem cell factor receptors. Cold Spring Harb. Perspect. Biol., 2013, 5(8), a009100.
[] [PMID: 23906712]
Fredriksson, L.; Li, H.; Eriksson, U. The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Rev., 2004, 15(4), 197-204.
[] [PMID: 15207811]
Calver, A.R.; Hall, A.C.; Yu, W-P.; Walsh, F.S.; Heath, J.K.; Betsholtz, C.; Richardson, W.D. Oligodendrocyte population dynamics and the role of PDGF in vivo. Neuron, 1998, 20(5), 869-882.
[] [PMID: 9620692]
Olsson, A.K.; Dimberg, A.; Kreuger, J.; Claesson-Welsh, L. VEGF receptor signalling - in control of vascular function. Nat. Rev. Mol. Cell Biol., 2006, 7(5), 359-371.
[] [PMID: 16633338]
Sherbet, G.V. Vascular Endothelial Growth Factor. Growth Factors and Their Receptors in Cell Differentiation, Cancer and Cancer Therapy. Elsevier; , 2011, pp. 55-64.
Koch, S.; Claesson-Welsh, L. Signal transduction by vascular endothelial growth factor receptors. Cold Spring Harb. Perspect. Med., 2012, 2(7), a006502-a006502.
[] [PMID: 22762016]
Shibuya, M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer, 2011, 2(12), 1097-1105.
[] [PMID: 22866201]
Miller, V.A.; Hirsh, V.; Cadranel, J.; Chen, Y-M.; Park, K.; Kim, S-W.; Zhou, C.; Su, W.C.; Wang, M.; Sun, Y.; Heo, D.S.; Crino, L.; Tan, E-H.; Chao, T-Y.; Shahidi, M.; Cong, X.J.; Lorence, R.M.; Yang, J.C-H. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol., 2012, 13(5), 528-538.
[] [PMID: 22452896]
Van Cutsem, E.; Lambrechts, D.; Prenen, H.; Jain, R.K.; Carmeliet, P. Lessons from the adjuvant bevacizumab trial on colon cancer: what next? J. Clin. Oncol., 2011, 29(1), 1-4.
[] [PMID: 21115866]
Price, T.J.; Peeters, M.; Kim, T.W.; Li, J.; Cascinu, S.; Ruff, P.; Suresh, A.S.; Thomas, A.; Tjulandin, S.; Zhang, K.; Murugappan, S.; Sidhu, R. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol., 2014, 15(6), 569-579.
[] [PMID: 24739896]
Hurwitz, H.I. Capecitabine, cetuximab, oxaliplatin, and bevacizumab in treating patients with metastatic or recurrent colorectal cancer that cannot be removed by surgery. NIH ClinicalTrials, NCT00290615, 2006 February 13; accessed at: September 23, 2020.
Jiang, T.; Zhou, C. Clinical activity of the mutant-selective EGFR inhibitor AZD9291 in patients with EGFR inhibitor-resistant non-small cell lung cancer. Transl. Lung Cancer Res., 2014, 3(6), 370-372.
[] [PMID: 25806323]
Karlovich, C.; Goldman, J.W.; Sun, J-M.; Mann, E.; Sequist, L.V.; Konopa, K.; Wen, W.; Angenendt, P.; Horn, L.; Spigel, D.; Soria, J-C.; Solomon, B.; Camidge, D.R.; Gadgeel, S.; Paweletz, C.; Wu, L.; Chien, S.; O’Donnell, P.; Matheny, S.; Despain, D.; Rolfe, L.; Raponi, M.; Allen, A.R.; Park, K.; Wakelee, H. Assessment of EGFR Mutation Status in Matched Plasma and Tumor Tissue of NSCLC Patients from a Phase I Study of Rociletinib (CO-1686). Clin. Cancer Res., 2016, 22(10), 2386-2395.
[] [PMID: 26747242]
Motzer, R.J.; Hutson, T.E.; Tomczak, P.; Michaelson, M.D.; Bukowski, R.M.; Rixe, O.; Oudard, S.; Negrier, S.; Szczylik, C.; Kim, S.T.; Chen, I.; Bycott, P.W.; Baum, C.M.; Figlin, R.A. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med., 2007, 356(2), 115-124.
[] [PMID: 17215529]
Guagnano, V.; Kauffmann, A.; Wöhrle, S.; Stamm, C.; Ito, M.; Barys, L.; Pornon, A.; Yao, Y.; Li, F.; Zhang, Y.; Chen, Z.; Wilson, C.J.; Bordas, V.; Le Douget, M.; Gaither, L.A.; Borawski, J.; Monahan, J.E.; Venkatesan, K.; Brümmendorf, T.; Thomas, D.M.; Garcia-Echeverria, C.; Hofmann, F.; Sellers, W.R.; Graus-Porta, D. FGFR genetic alterations predict for sensitivity to NVP-BGJ398, a selective pan-FGFR inhibitor. Cancer Discov., 2012, 2(12), 1118-1133.
[] [PMID: 23002168]
Novartis (Novartis Pharmaceuticals). FGF401 in HCC and solid tumors characterized by positive FGFR4 and KLB expression. NIH ClinicalTrials, NCT02325739, December 25;2014 accessed at: September 23, 2020
Nandi, S.; Bagchi, M.C. EGFr, FGFr and PDGFr: Emerging Targets for Anticancer Drug Design. J. Cancer Res., 2016, 5, 99-108.
Kamba, T.; McDonald, D.M. Mechanisms of adverse effects of anti-VEGF therapy for cancer. Br. J. Cancer, 2007, 96(12), 1788-1795.
[] [PMID: 17519900]
Matsui, J.; Funahashi, Y.; Uenaka, T.; Watanabe, T.; Tsuruoka, A.; Asada, M. Multi-kinase inhibitor E7080 suppresses lymph node and lung metastases of human mammary breast tumor MDA-MB-231 via inhibition of vascular endothelial growth factor-receptor (VEGF-R) 2 and VEGF-R3 kinase. Clin. Cancer Res., 2008, 14(17), 5459-5465.
[] [PMID: 18765537]
Martin, P.; Oliver, S.; Kennedy, S.J.; Partridge, E.; Hutchison, M.; Clarke, D.; Giles, P. Pharmacokinetics of vandetanib: three phase I studies in healthy subjects. Clin. Ther., 2012, 34(1), 221-237.
[] [PMID: 22206795]
Zivi, A.; Cerbone, L.; Recine, F.; Sternberg, C.N. Safety and tolerability of pazopanib in the treatment of renal cell carcinoma. Expert Opin. Drug Saf., 2012, 11(5), 851-859.
[] [PMID: 22861374]
Rini, B.; Rixe, O.; Bukowski, R.; Michaelson, M.D.; Wilding, G.; Bolte, G.H.; Steinfeldt, H.; Reich, S.D.; Motzer, R. AG-013736, a multi-target tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a Phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC). J. Clin. Oncol., 2005, 23(16S), 4509.
Kurzrock, R.; Sherman, S.I.; Ball, D.W.; Forastiere, A.A.; Cohen, R.B.; Mehra, R.; Pfister, D.G.; Cohen, E.E.; Janisch, L.; Nauling, F.; Hong, D.S.; Ng, C.S.; Ye, L.; Gagel, R.F.; Frye, J.; Müller, T.; Ratain, M.J.; Salgia, R. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J. Clin. Oncol., 2011, 29(19), 2660-2666.
[] [PMID: 21606412]
Saxena, A.K.; Bhunia, S.S. Development of VEGFR Inhibitors as Antiangiogenic Agents.Med. Chem. Rev., 51, 299-310.
Gupta, A.K.; Bhunia, S.S.; Balaramnavar, V.M.; Saxena, A.K. Pharmacophore modelling, molecular docking and virtual screening for EGFR (HER 1) tyrosine kinase inhibitors. SAR QSAR Environ. Res., 2011, 22(3), 239-263.
[] [PMID: 21400356]
Nandi, S.; Bagchi, M.C. QSAR of aminopyrido[2,3-d]pyrimidin-7-yl derivatives: anticancer drug design by computed descriptors. J. Enzyme Inhib. Med. Chem., 2009, 24(4), 937-948.
[] [PMID: 19555178]
Nandi, S.; Bagchi, M.C. 3D-QSAR and molecular docking studies of 4-anilinoquinazoline derivatives: a rational approach to anticancer drug design. Mol. Divers., 2010, 14(1), 27-38.
[] [PMID: 19330460]
Nandi, S.; Bagchi, M.C. In silico design of potent EGFR kinase inhibitors by structure based screening of combinatorial libraries. Mol. Simul., 2011, 37, 196-209.
Cambie, R.C.; Madden, R.J.; Parnell, J.C. Chemistry of the Podocarpaceae. XXVIII. Constituents of some Podocarpus and other species. Aust. J. Chem., 1971, 24, 217-221.
Reddy, P.J.; Ray, S.; Sathe, G.J.; Gajbhiye, A.; Prasad, T.S.K.; Rapole, S.; Panda, D.; Srivastava, S. A comprehensive proteomic analysis of totarol induced alterations in Bacillus subtilis by multipronged quantitative proteomics. J. Proteomics, 2015, 114, 247-262.
[] [PMID: 25464363]
Olivero-Acosta, M.; Maldonado-Rojas, W.; Olivero-Verbel, J. Natural Products as Chemopreventive Agents by Potential Inhibition of the Kinase Domain in ErbB Receptors. Molecules, 2017, 22(2), 308.
[] [PMID: 28218686]
Paik, S.Y.; Koh, K.H.; Beak, S.M.; Paek, S.H.; Kim, J.A. The essential oils from Zanthoxylum schinifolium pericarp induce apoptosis of HepG2 human hepatoma cells through increased production of reactive oxygen species. Biol. Pharm. Bull., 2005, 28(5), 802-807.
[] [PMID: 15863882]
Zou, J.; Lei, T.; Guo, P.; Yu, J.; Xu, Q.; Luo, Y.; Ke, R.; Huang, D. Mechanisms shaping the role of ERK1/2 in cellular senescence (Review). Mol. Med. Rep., 2019, 19(2), 759-770.
[] [PMID: 30535440]
Gasparotto, J.; Somensi, N.; Kunzler, A.; Girardi, C.S.; de Bittencourt Pasquali, M.A.; Ramos, V.M.; Simoes-Pires, A.; Quintans-Junior, L.J.; Branco, A.; Moreira, J.C.; Gelain, D.P. Hecogenin acetate inhibits reactive oxygen species production and induces cell cycle arrest and senescence in the A549 human lung cancer cell line. Anticancer. Agents Med. Chem., 2014, 14(8), 1128-1135.
[] [PMID: 25115457]
Rouseff, R.L.; Martin, S.F.; Youtsey, C.O. Quantitative survey of narirutin, naringin, hesperidin, and neo hesperidin in citrus. J. Agric. Food Chem., 1987, 35(6), 1027-1030.
Devi, K.P.; Rajavel, T.; Nabavi, S.F.; Setzer, W.N.; Ahmadi, A.; Mansouri, K.; Nabavi, S.M. Hesperidin: A promising anticancer agent from nature. Ind. Crops Prod., 2015, 76, 582-589.
Golonko, A.; Lewandowska, H.; Świsłocka, R.; Jasińska, U.T.; Priebe, W.; Lewandowski, W. Curcumin as tyrosine kinase inhibitor in cancer treatment. Eur. J. Med. Chem., 2019, 181, 111512.
[] [PMID: 31404861]
Starok, M.; Preira, P.; Vayssade, M.; Haupt, K.; Salomé, L.; Rossi, C. EGFR Inhibition by Curcumin in Cancer Cells: A Dual Mode of Action. Biomacromolecules, 2015, 16(5), 1634-1642.
[] [PMID: 25893361]
Esfahani, K; Boodaghians, L; Kasymjanova, G. A phase I open prospective cohort trial of curcumin plus tyrosine kinase inhibitors for EGFR-mutant advanced non-small cell lung cancer. J. Clin. Oncol., 2019, 37(15_suppl), e20611.
Ma, Y-C.; Li, C.; Gao, F.; Xu, Y.; Jiang, Z-B.; Liu, J-X.; Jin, L-Y. Epigallocatechin gallate inhibits the growth of human lung cancer by directly targeting the EGFR signaling pathway. Oncol. Rep., 2014, 31(3), 1343-1349.
[] [PMID: 24366444]
Leone, M.; Zhai, D.; Sareth, S.; Kitada, S.; Reed, J.C.; Pellecchia, M. Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins. Cancer Res., 2003, 63(23), 8118-8121.
[PMID: 14678963]
Wang, H.; Khor, T.O.; Shu, L.; Su, Z.Y.; Fuentes, F.; Lee, J-H.; Kong, A-N.T. Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability. Anticancer. Agents Med. Chem., 2012, 12(10), 1281-1305.
[] [PMID: 22583408]
Perkin, A.G.; Newbury, F.G. LXXIX.—The colouring matters contained in dyer’s broom (Genista tinctoria) and heather (Calluna vulgaris). J. Chem. Soc. Trans., 1899, 75, 830-839.
Tuli, H.S.; Tuorkey, M.J.; Thakral, F.; Sak, K.; Kumar, M.; Sharma, A.K.; Sharma, U.; Jain, A.; Aggarwal, V.; Bishayee, A. Molecular Mechanisms of Action of Genistein in Cancer: Recent Advances. Front. Pharmacol., 2019, 10, 1336.
[] [PMID: 31866857]
Ronis, M.J.J. Effects of soy containing diet and isoflavones on cytochrome P450 enzyme expression and activity. Drug Metab. Rev., 2016, 48(3), 331-341.
[] [PMID: 27440109]
Bailey, H.H. National Cancer Institute (NCI). Phase II study of isoflavone G-2535 (Genistein) in patients with bladder cancer. NIHClinicalTrials, NCT00118040, July 11, 2005. accessed at: September 23, 2020
Efferth, T. Natural Products as Inhibitors of Epidermal Growth Factor Receptor. For. Immunopathol. Dis. Therap., 2011, 2(4), 281-301.
Gadgeel, S.M.; Ali, S.; Philip, P.A.; Wozniak, A.; Sarkar, F.H. Genistein enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitors and inhibits nuclear factor kappa B in nonsmall cell lung cancer cell lines. Cancer, 2009, 115(10), 2165-2176.
[] [PMID: 19288574]
Sang, S. Tea: chemistry and processing. In: Encyclopedia of Food and Health; Caballero, B.; Finglas, P.M.; Toldrá, F, Eds.; Academic Press 2016, 268-272.
Mizuno, H.; Cho, Y-Y.; Zhu, F.; Ma, W-Y.; Bode, A.M.; Yang, C.S.; Ho, C-T.; Dong, Z. Theaflavin-3, 3′-digallate induces epidermal growth factor receptor downregulation. Mol. Carcinog., 2006, 45(3), 204-212.
[] [PMID: 16353237]
Quercetin (biochemistry). Encyclopædia Britannica., accessed at: September 25, 2020.
Arunakaran, J. Quercetin, a Natural Dietary Flavonoid Inhibits, Reverses, Retards Tumorigenesis in Prostate and Breast Cancer. Ann. Pharmacol. Pharm, 2017, 2(8), 1085.
Lee, L-T.; Huang, Y-T.; Hwang, J-J.; Lee, P-P.H.; Ke, F-C.; Nair, M.P.; Kanadaswam, C.; Lee, M-T. Blockade of the epidermal growth factor receptor tyrosine kinase activity by quercetin and luteolin leads to growth inhibition and apoptosis of pancreatic tumor cells. Anticancer Res., 2002, 22(3), 1615-1627.
[PMID: 12168845]
Glade Bender, J.; Cooney, E.M.; Kandel, J.J.; Yamashiro, D.J. Vascular remodeling and clinical resistance to antiangiogenic cancer therapy. Drug Resist. Updat., 2004, 7(4-5), 289-300.
[] [PMID: 15533766]
Benjamin, L.E.; Hemo, I.; Keshet, E. A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development, 1998, 125(9), 1591-1598.
[PMID: 9521897]
Gerhardt, H.; Betsholtz, C. Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res., 2003, 314(1), 15-23.
[] [PMID: 12883993]
Hellström, M.; Kalén, M.; Lindahl, P.; Abramsson, A.; Betsholtz, C. Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development, 1999, 126(14), 3047-3055.
[PMID: 10375497]
Lamy, S.; Beaulieu, E.; Labbé, D.; Bédard, V.; Moghrabi, A.; Barrette, S.; Gingras, D.; Béliveau, R. Delphinidin, a dietary anthocyanidin, inhibits platelet-derived growth factor ligand/receptor (PDGF/PDGFR) signaling. Carcinogenesis, 2008, 29(5), 1033-1041.
[] [PMID: 18339683]
Sivasankar, S.; Lavanya, R.; Brindha, P.; Angayarkanni, N. Aqueous and alcoholic extracts of Triphala and their active compounds chebulagic acid and chebulinic acid prevented epithelial to mesenchymal transition in retinal pigment epithelial cells, by inhibiting SMAD-3 phosphorylation. PLoS One, 2015, 10(3), e0120512.
[] [PMID: 25793924]
Yi, Z.C.; Liu, Y.Z.; Li, H.X.; Wang, Z. Chebulinic acid and tellimagrandin I inhibit DNA strand breaks by hydroquinone/Cu(II) and H(2)O(2)/Cu(II), but potentiate DNA strand breaks by H(2)O(2)/Fe(II). Toxicol. In Vitro, 2009, 23(4), 667-673.
[] [PMID: 19328845]
Afshari, A.R.; Sadeghnia, H.R.; Mollazadeh, H. A Review on Potential Mechanisms of Terminalia chebula in Alzheimer’s Disease. Adv. Pharmacol. Sci., 2016, 2016, 8964849.
[] [PMID: 26941792]
Song, I-S.; Jeong, Y.J.; Park, J.H.; Shim, S.; Jang, S-W. Chebulinic acid inhibits smooth muscle cell migration by suppressing PDGF-Rβ phosphorylation and inhibiting matrix metalloproteinase-2 expression. Sci. Rep., 2017, 7(1), 11797.
[] [PMID: 28924208]
Seigler, D.S. Plant Secondary Metabolism Springer Science & Business Media Boston; , 1998.
Daniel, E.M.; Kropnick, A.S.; Heur, Y.H.; Blinzler, J.A.; Nims, R.W.; Stoner, G.D. Extraction, stability, and quantitation of ellagic acid invarious fruit and nuts. J. Food Compos. Anal., 1990, 2, 338-349.
Labrecque, L.; Lamy, S.; Chapus, A.; Mihoubi, S.; Durocher, Y.; Cass, B.; Bojanowski, M.W.; Gingras, D.; Béliveau, R. Combined inhibition of PDGF and VEGF receptors by ellagic acid, a dietary-derived phenolic compound. Carcinogenesis, 2005, 26(4), 821-826.
[] [PMID: 15661805]
Mangels, A.R.; Holden, J.M.; Beecher, G.R.; Forman, M.R.; Lanza, E. Carotenoid content of fruits and vegetables: an evaluation of analytic data. J. Am. Diet. Assoc., 1993, 93(3), 284-296.
[] [PMID: 8440826]
Sesso, H.D. Carotenoids and cardiovascular disease: what research gaps remain? Curr. Opin. Lipidol., 2006, 17(1), 11-16.
[] [PMID: 16407710]
Lo, H-M.; Tsai, Y-J.; Du, W-Y.; Tsou, C-J.; Wu, W-B. A naturally occurring carotenoid, lutein, reduces PDGF and H₂O₂ signaling and compromised migration in cultured vascular smooth muscle cells. J. Biomed. Sci., 2012, 19, 18.
[] [PMID: 22313606]
Ohio State University. Compound in Mediterranean diet makes cancer cells 'mortal'. ScienceDaily. accessed at: September 25, 2020.
López-Lázaro, M. Distribution and biological activities of the flavonoid luteolin. Mini Rev. Med. Chem., 2009, 9(1), 31-59.
[] [PMID: 19149659]
Lamy, S.; Bédard, V.; Labbé, D.; Sartelet, H.; Barthomeuf, C.; Gingras, D.; Béliveau, R. The dietary flavones apigenin and luteolin impair smooth muscle cell migration and VEGF expression through inhibition of PDGFR-β phosphorylation. Cancer Prev. Res. (Phila.), 2008, 1(6), 452-459.
[] [PMID: 19138992]
Heldin, C.H.; Ostman, A.; Rönnstrand, L. Signal transduction via platelet-derived growth factor receptors. Biochim. Biophys. Acta, 1998, 1378(1), F79-F113.
[] [PMID: 9739761]
Huang, C.; Jacobson, K.; Schaller, M.D. MAP kinases and cell migration. J. Cell Sci., 2004, 117(Pt 20), 4619-4628.
[] [PMID: 15371522]
Zhan, Y.; Kim, S.; Izumi, Y.; Izumiya, Y.; Nakao, T.; Miyazaki, H.; Iwao, H. Role of JNK, p38, and ERK in platelet-derived growth factor-induced vascular proliferation, migration, and gene expression. Arterioscler. Thromb. Vasc. Biol., 2003, 23(5), 795-801.
[] [PMID: 12637337]
Abramsson, A.; Lindblom, P.; Betsholtz, C. Endothelial and nonendothelial sources of PDGF-B regulate pericyte recruitment and influence vascular pattern formation in tumors. J. Clin. Invest., 2003, 112(8), 1142-1151.
[] [PMID: 14561699]
Reinmuth, N.; Liu, W.; Jung, Y.D.; Ahmad, S.A.; Shaheen, R.M.; Fan, F.; Bucana, C.D.; McMahon, G.; Gallick, G.E.; Ellis, L.M. Induction of VEGF in perivascular cells defines a potential paracrine mechanism for endothelial cell survival. FASEB J., 2001, 15(7), 1239-1241.
[] [PMID: 11344100]
Raffo, A.; Leonardi, C.; Fogliano, V.; Ambrosino, P.; Salucci, M.; Gennaro, L.; Bugianesi, R.; Giuffrida, F.; Quaglia, G. Nutritional value of cherry tomatoes (Lycopersicon esculentum Cv. Naomi F1) harvested at different ripening stages. J. Agric. Food Chem., 2002, 50(22), 6550-6556.
[] [PMID: 12381148]
Wu, W-B.; Chiang, H-S.; Fang, J-Y.; Hung, C-F. Inhibitory effect of lycopene on PDGF-BB-induced signalling and migration in human dermal fibroblasts: a possible target for cancer. Biochem. Soc. Trans., 2007, 35(Pt 5), 1377-1378.
[] [PMID: 17956356]
Takahashi, H.; Nguyen, B.C.Q.; Uto, Y.; Shahinozzaman, M.; Tawata, S.; Maruta, H. 1,2,3-Triazolyl esterization of PAK1-blocking propolis ingredients, artepillin C (ARC) and caffeic acid (CA), for boosting their anti-cancer/anti-PAK1 activities along with cell-permeability. Drug Discov. Ther., 2017, 11(2), 104-109.
[] [PMID: 28442677]
Ho, H.C.; Chang, H.C.; Ting, C.T.; Kuo, C.Y.; Yang, V.C. Caffeic acid phenethyl ester inhibits proliferation and migration, and induces apoptosis in platelet-derived growth factor-BB-stimulated human coronary smooth muscle cells. J. Vasc. Res., 2012, 49(1), 24-32.
[] [PMID: 21986482]
Hussain, S.; Slevin, M.; Ahmed, N.; West, D.; Choudhary, M.I.; Naz, H.; Gaffney, J. Stilbene glycosides are natural product inhibitors of FGF-2-induced angiogenesis. BMC Cell Biol., 2009, 10, 30.
[] [PMID: 19389252]
Medjakovic, S.; Jungbauer, A. Red clover isoflavones biochanin A and formononetin are potent ligands of the human aryl hydrocarbon receptor. J. Steroid Biochem. Mol. Biol., 2008, 108(1-2), 171-177.
[] [PMID: 18060767]
Wu, X.Y.; Xu, H.; Wu, Z.F.; Chen, C.; Liu, J.Y.; Wu, G.N.; Yao, X.Q.; Liu, F.K.; Li, G.; Shen, L. Formononetin, a novel FGFR2 inhibitor, potently inhibits angiogenesis and tumor growth in preclinical models. Oncotarget, 2015, 6(42), 44563-44578.
[] [PMID: 26575424]
Meyer, A.N.; McAndrew, C.W.; Donoghue, D.J. Nordihydroguaiaretic Acid Inhibits an Activated FGFR3 Mutant, and Blocks Downstream Signaling in Multiple Myeloma Cells. Cancer Res., 2008, 68(18), 7362-7370.
[] [PMID: 18794123]
Wu, J.; Ji, J.; Weng, B.; Qiu, P.; Kanchana, K.; Wei, T.; Wang, Y.; Cai, Y.; Li, X.; Liang, G. Discovery of novel non-ATP competitive FGFR1 inhibitors and evaluation of their anti-tumor activity in non-small cell lung cancer in vitro and in vivo. Oncotarget, 2014, 5(12), 4543-4553.
[] [PMID: 24980830]
Wang, Y.; Ma, W.; Zheng, W. Deguelin, a novel anti-tumorigenic agent targeting apoptosis, cell cycle arrest and anti-angiogenesis for cancer chemoprevention. Mol. Clin. Oncol., 2013, 1(2), 215-219.
[] [PMID: 24649149]
Semenza, G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer, 2003, 3(10), 721-732.
[] [PMID: 13130303]
Bai, X.; Cerimele, F.; Ushio-Fukai, M.; Waqas, M.; Campbell, P.M.; Govindarajan, B.; Der, C.J.; Battle, T.; Frank, D.A.; Ye, K.; Murad, E.; Dubiel, W.; Soff, G.; Arbiser, J.L. Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J. Biol. Chem., 2003, 278(37), 35501-35507.
[] [PMID: 12816951]
Babykutty, S.; Priya, P.S. Nandini, R.J.; Suresh Kumar, M.A.; Nair, M.S.; Srinivas, P.; Gopala, S. Nimbolide retards tumor cell migration, invasion, and angiogenesis by downregulating MMP-2/9 expression via inhibiting ERK1/2 and reducing DNA-binding activity of NF-kB in colon cancer cells. Mol. Carcinog., 2012, 51, 475-490.
[] [PMID: 21678498]
Gururaj, A.E.; Belakavadi, M.; Venkatesh, D.A.; Marmé, D.; Salimath, B.P. Molecular mechanisms of anti-angiogenic effect of curcumin. Biochem. Biophys. Res. Commun., 2002, 297(4), 934-942.
[] [PMID: 12359244]
Hamsa, T.P.; Kuttan, G. Harmine inhibits tumour specific neo-vessel formation by regulating VEGF, MMP, TIMP and pro-inflammatory mediators both in vivo and in vitro. Eur. J. Pharmacol., 2010, 649(1-3), 64-73.
[] [PMID: 20858484]
Pang, X.; Yi, Z.; Zhang, X.; Sung, B.; Qu, W.; Lian, X.; Aggarwal, B.B.; Liu, M. Acetyl-11-keto-beta-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis. Cancer Res., 2009, 69(14), 5893-5900.
[] [PMID: 19567671]
Lu, K.; Basu, S. The natural compound chebulagic acid inhibits vascular endothelial growth factor A mediated regulation of endothelial cell functions. Sci. Rep., 2015, 5, 9642.
[] [PMID: 25859636]
Lu, K.; Chakroborty, D.; Sarkar, C.; Lu, T.; Xie, Z.; Liu, Z.; Basu, S. Triphala and its active constituent chebulinic acid are natural inhibitors of vascular endothelial growth factor-a mediated angiogenesis. PLoS One, 2012, 7(8), e43934.
[] [PMID: 22937129]
Singh, D.P.; Govindarajan, R.; Rawat, A.K.S. High-performance liquid chromatography as a tool for the chemical standardisation of Triphala--an Ayurvedic formulation. Phytochem. Anal., 2008, 19(2), 164-168.
[] [PMID: 17879225]
Pawar, V.; Lahorkar, P.; Anantha Narayana, D.B. Development of a RP-HPLCmethod for analysis of Triphala Curna and its applicability to test variations in Triphala Curna preparations. Indian J. Pharm. Sci., 2009, 71(4), 382-386.
[] [PMID: 20502543]
Radulović, N.; Quang, D.N.; Hashimoto, T.; Nukada, M.; Asakawa, Y. Terrestrins A-G: p-terphenyl derivatives from the inedible mushroom Thelephora terrestris. Phytochemistry, 2005, 66(9), 1052-1059.
[] [PMID: 15896375]
Xie, C.; Koshino, H.; Esumi, Y.; Takahashi, S.; Yoshikawa, K.; Abe, N. Vialinin A, a novel 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenger from an edible mushroom in China. Biosci. Biotechnol. Biochem., 2005, 69(12), 2326-2332.
[] [PMID: 16377890]
Sonowal, H.; Shukla, K.; Kota, S.; Saxena, A.; Ramana, K.V. Vialinin A, an Edible Mushroom-Derived p-Terphenyl Antioxidant, Prevents VEGF-Induced Neovascularization In Vitro and In Vivo. Oxid. Med. Cell. Longev., 2018, 2018, 1052102.
[] [PMID: 29541344]
Zhou, X.; Yue, G.G-L.; Liu, M.; Zuo, Z.; Lee, J.K.; Li, M.; Tsui, S.K.; Fung, K.P.; Sun, H.; Pu, J.; Lau, C.B. Eriocalyxin B, a natural diterpenoid, inhibited VEGF-induced angiogenesis and diminished angiogenesis-dependent breast tumor growth by suppressing VEGFR-2 signaling. Oncotarget, 2016, 7(50), 82820-82835.
[] [PMID: 27756875]
Yurugi, H.; Zhuang, Y.; Siddiqui, F.A.; Liang, H.; Rosigkeit, S.; Zeng, Y.; Abou-Hamdan, H.; Bockamp, E.; Zhou, Y.; Abankwa, D.; Zhao, W.; Désaubry, L.; Rajalingam, K. A subset of flavaglines inhibits KRAS nanoclustering and activation. J. Cell Sci., 2020, 133(12), jcs244111.
[] [PMID: 32501281]
Yang, J.; Li, B.; He, Q-Y. Significance of prohibitin domain family in tumorigenesis and its implication in cancer diagnosis and treatment. Cell Death Dis., 2018, 9(6), 580.
[] [PMID: 29784973]
Yurugi, H.; Marini, F.; Weber, C.; David, K.; Zhao, Q.; Binder, H.; Désaubry, L.; Rajalingam, K. Targeting prohibitins with chemical ligands inhibits KRAS-mediated lung tumours. Oncogene, 2017, 36(42), 5914.
[] [PMID: 28846116]

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