Skip to main content
SpringerLink
Log in

Cancer Chemopreventive Potential of Epidermal Growth Factor Receptor Inhibitors from Natural Products

  • Chapter
  • First Online:
Natural Products for Cancer Chemoprevention

Abstract

Receptor tyrosine kinases (RTKs) are cell membrane-anchored receptors that bind to growth factors, cytokines, and hormones for signal transduction and regulate various signaling cascades. Among the diverse RTKs, epidermal growth factor receptor (EGFR) has been suggested to be upstream of major signaling pathways and regarded as a therapeutic target in cancer metastasis, tumorigenesis or drug resistance. The EGFR belongs to the ErbB RTK family and is significantly overexpressed or mutated in various epithelial malignancies. Many anticancer drugs are used to target EGFR (EGFR tyrosine kinase inhibitors, EGFR TKIs) in the clinic, but critical limitations of those drugs persist. Targeted therapies have improved the prognosis and survival of cancer patients. However, large numbers of patients treated with EFGR TKIs acquire drug resistance, for which multiple mechanisms have been suggested. Therefore, there remains an important need to develop antitumor agents targeting EGFR through the use of natural products with high efficacy. A variety of natural products have been investigated to identify novel antitumor agents that could regulate EGFR via different mechanisms. In addition, combination approaches employing natural products and molecular target therapies have been widely discussed. In the present review, we will summarize the critical roles of EGFR in tumor progression and provide a list of natural products that regulate the EGFR signaling pathway. Targeting EGFR signaling using natural products with different mechanisms may effectively overcome EFGR TKI acquired drug resistance and provide an additional strategy in the treatment of cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Al-Akhrass H, Naves T, Vincent F, Magnaudeix A, Durand K, Bertin F, Melloni B, Jauberteau MO, Lalloue F (2017) Sortilin limits EGFR signaling by promoting its internalization in lung cancer. Nat Commun 8:1182

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arora A, Scholar EM (2005) Role of tyrosine kinase inhibitors in cancer therapy. J Pharm Exp Ther 315:971–979

    Article  CAS  Google Scholar 

  • Baba Y, Maeda T, Suzuki A, Takada S, Fujii M, Kato Y (2017) Deguelin potentiates apoptotic activity of an EGFR tyrosine kinase inhibitor (AG1478) in PIK3CA-mutated head and neck squamous cell carcinoma. Int J Mol Sci 18:E262

    Article  PubMed  CAS  Google Scholar 

  • Bach D-H, Lee SK (2018) Long noncoding RNAs in cancer cells. Cancer Lett 419:152–166

    Article  CAS  PubMed  Google Scholar 

  • Bach D-H, Kim D, Bae SY, Kim WK, Hong J-Y, Lee H-J, Rajasekaran N, Kwon S, Fan Y, Luu T-T-T, Shin YK, Lee J, Lee SK (2018a) Targeting nicotinamide N-methyltransferase and miR-449a in EGFR-TKI-resistant non-small-cell lung cancer cells. Mol Ther – Nucleic Acids 11:455–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bach D-H, Luu T-T-T, Kim D, An YJ, Park HJ, Park S, Lee SK (2018b) BMP4 upregulation is associated with acquired drug resistance and fatty acid metabolism in EGFR-mutant non-small cell lung cancer cells. Mol Ther – Nucleic Acids 12:817–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bae SY, Hong JY, Lee HJ, Park HJ, Lee SK (2015) Targeting the degradation of AXL receptor tyrosine kinase to overcome resistance in gefitinib-resistant non-small cell lung cancer. Oncotarget 6:10146–10160

    Article  PubMed  PubMed Central  Google Scholar 

  • Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, Chitale D, Motoi N, Szoke J, Broderick S, Balak M, Chang WC, Yu CJ, Gazdar A, Pass H, Rusch V, Gerald W, Huang SF, Yang PC, Miller V, Ladanyi M, Yang CH, Pao W (2007) MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 104:20932–20937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beck S, Jin X, Sohn YW, Kim JK, Kim SH, Yin J, Pian X, Kim SC, Nam DH, Choi YJ, Kim H (2011) Telomerase activity-independent function of TERT allows glioma cells to attain cancer stem cell characteristics by inducing EGFR expression. Mol Cells 31:9–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang CC, Yang MH, Lin BR, Chen ST, Pan SH, Hsiao M, Lai TC, Lin SK, Jeng YM, Chu CY, Chen RH, Yang PC, Chin YE, Kuo ML (2013) CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation. Cell Death Differ 20:443–455

    Article  CAS  PubMed  Google Scholar 

  • Chen HH, Zhou HJ, Wu GD, Lou XE (2004) Inhibitory effects of artesunate on angiogenesis and on expressions of vascular endothelial growth factor and VEGF receptor KDR/flk-1. Pharmacology 71:1–9

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Henson ES, Xiao W, Huang D, Mcmillan-Ward EM, Israels SJ, Gibson SB (2016) Tyrosine kinase receptor EGFR regulates the switch in cancer cells between cell survival and cell death induced by autophagy in hypoxia. Autophagy 12:1029–1046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chien CM, Lin KL, Su JC, Chang LS, Lin SR (2009) Inactivation of epidermal growth factor receptor and downstream pathways in oral squamous cell carcinoma Ca9-22 cells by cardiotoxin III from Naja naja atra. J Nat Prod 72:1735–1740

    Article  CAS  PubMed  Google Scholar 

  • Cho BC, Chewaskulyong B, Lee KH, Dechaphunkul A, Sriuranpong V, Imamura F, Ohe Y, Nogami N, Kurata T, Okamoto I, Zhou C, Cheng Y, Cho EK, Jye VP, Lee JS, Mann H, Saggese M, Reungwetwattana T (2017) Osimertinib vs standard of care (SoC) EGFR-TKI as first-line treatment in patients with EGFR-TKI sensitising mutation (EGFRm) positive advanced non-small cell lung cancer (NSCLC): FLAURA Asian subset. Ann Oncol 28:190–190

    Article  Google Scholar 

  • Comis RL (2005) The current situation: Erlotinib (Tarceva (R)) and gefitinib (Iressa (R)) in non-small cell lung cancer. Oncologist 10:467–470

    Article  CAS  PubMed  Google Scholar 

  • Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, Hughes G, Rahi A, Jacobs VN, Red Brewer M, Ichihara E, Sun J, Jin H, Ballard P, Al-Kadhimi K, Rowlinson R, Klinowska T, Richmond GH, Cantarini M, Kim DW, Ranson MR, Pao W (2014) AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 4:1046–1061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cufi S, Bonavia R, Vazquez-Martin A, Oliveras-Ferraros C, Corominas-Faja B, Cuyas E, Martin-Castillo B, Barrajon-Catalan E, Visa J, Segura-Carretero A, Joven J, Bosch-Barrera J, Micol V, Menendez JA (2013) Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR-21/low miR-200c signature in vivo. Sci Rep 3:2459

    Article  PubMed  PubMed Central  Google Scholar 

  • Culy CR, Faulds D (2002) Gefitinib. Drugs 62:2237–2248. discussion 2249-50

    Article  CAS  PubMed  Google Scholar 

  • Dai X, Li RZ, Jiang ZB, Wei CL, Luo LX, Yao XJ, Li GP, Leung ELH (2018) Honokiol inhibits proliferation, invasion and induces apoptosis through targeting Lyn kinase in human lung adenocarcinoma cells. Front Pharmacol 9:558

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Demain AL, Vaishnav P (2011) Natural products for cancer chemotherapy. Microbial Biotechnol 4:687–699

    Article  Google Scholar 

  • Dogan S, Shen R, Ang DC, Johnson ML, D’angelo SP, Paik PK, Brzostowski EB, Riely GJ, Kris MG, Zakowski MF, Ladanyi M (2012) Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers. Clin Cancer Res 18:6169–6177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duc-Hiep B, Sang Kook L (2018) The potential impacts of tylophora alkaloids and their derivatives in modulating inflammation, viral infections, and cancer. Curr Med Chem 25:1–16

    Article  Google Scholar 

  • Efferth T, Ramirez T, Gebhart E, Halatsch ME (2004) Combination-treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774. Biochem Pharmacol 67:1689–1700

    Article  CAS  PubMed  Google Scholar 

  • Engelman JA, Settleman J (2008) Acquired resistance to tyrosine kinase inhibitors during cancer therapy. Curr Opin Genet Dev 18:73–79

    Article  CAS  PubMed  Google Scholar 

  • Ferguson KM, Berger MB, Mendrola JM, Cho HS, Leahy DJ, Lemmon MA (2003) EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Mol Cell 11:507–517

    Article  CAS  PubMed  Google Scholar 

  • Fung C, Chen X, Grandis JR, Duvvuri U (2012) EGFR tyrosine kinase inhibition induces autophagy in cancer cells. Cancer Biol Ther 13:1417–1424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gadelha IC, Fonseca NB, Oloris SC, Melo MM, Soto-Blanco B (2014) Gossypol toxicity from cottonseed products. ScientificWorldJournal 2014:231635

    PubMed  PubMed Central  Google Scholar 

  • Gerhauser C, Lee SK, Kosmeder JW, Moriarty RM, Hamel E, Mehta RG, Moon RC, Pezzuto JM (1997) Regulation of ornithine decarboxylase induction by deguelin, a natural product cancer chemopreventive agent. Cancer Res 57:3429–3435

    CAS  PubMed  Google Scholar 

  • Gomez D, de Rosa A, Addison A, Brooks A, Malik HZ, Cameron IC (2013) Cetuximab therapy in the treatment of metastatic colorectal cancer: the future frontier? Int J Surg 11:507–513

    Article  CAS  PubMed  Google Scholar 

  • Gu HR, Park SC, Choi SJ, Lee JC, Kim YC, Han CJ, Kim J, Yang KY, Kim YJ, Noh GY, No SH, Jeong JH (2015) Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells. Clin Mol Hepatol 21:49–59

    Article  PubMed  PubMed Central  Google Scholar 

  • He L, Liu X, Yang J, Li W, Liu S, Liu X, Yang Z, Ren J, Wang Y, Shan L, Guan C, Pei F, Lei L, Zhang Y, Yi X, Yang X, Liang J, Liu R, Sun L, Shang Y (2018) Imbalance of the reciprocally inhibitory loop between the ubiquitin-specific protease USP43 and EGFR/PI3K/AKT drives breast carcinogenesis. Cell Res 28:934–951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hong JY, Nam JW, Seo EK, Lee SK (2010) Daphnane diterpene esters with anti-proliferative activities against human lung cancer cells from Daphne genkwa. Chem Pharm Bull (Tokyo) 58:234–237

    Article  CAS  Google Scholar 

  • Hong JY, Chung HJ, Lee HJ, Park HJ, Lee SK (2011) Growth inhibition of human lung cancer cells via down-regulation of epidermal growth factor receptor signaling by yuanhuadine, a daphnane diterpene from Daphne genkwa. J Nat Prod 74:2102–2108

    Article  CAS  PubMed  Google Scholar 

  • Hu J, Qian Y, Peng L, Ma L, Qiu T, Liu Y, Li X, Chen X (2018) Long noncoding RNA EGFR-AS1 promotes cell proliferation by increasing EGFR mRNA stability in gastric cancer. Cell Physiol Biochem 49:322–334

    Article  CAS  PubMed  Google Scholar 

  • Huang F, Shi Q, Li Y, Xu L, Xu C, Chen F, Wang H, Liao H, Chang Z, Liu F, Zhang XH, Feng XH, Han JJ, Luo S, Chen YG (2018a) HER2/EGFR-AKT signaling switches TGF-beta from inhibiting cell proliferation to promoting cell migration in breast cancer. Cancer Res 78:6073–6085

    Article  CAS  PubMed  Google Scholar 

  • Huang L, Wen C, Yang X, Lou Q, Wang X, Che J, Chen J, Yang Z, Wu X, Huang M, Lan P, Wang L, Iwamoto A, Wang J, Liu H (2018b) PEAK1, acting as a tumor promoter in colorectal cancer, is regulated by the EGFR/KRas signaling axis and miR-181d. Cell Death Dis 9:271

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218–220

    Article  CAS  PubMed  Google Scholar 

  • Ju X, Yang X, Yan T, Chen H, Song Z, Zhang Z, Wu W, Wang Y (2018) EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy. Clin Exp Pharmacol Physiol

    Google Scholar 

  • Kang DY, Sp N, Kim DH, Joung YH, Lee HG, Park YM, Yang YM (2018) Salidroside inhibits migration, invasion and angiogenesis of MDAMB 231 TNBC cells by regulating EGFR/Jak2/STAT3 signaling via MMP2. Int J Oncol 53:877–885

    CAS  PubMed  Google Scholar 

  • Keller S, Schmidt MHH (2017) EGFR and EGFRvIII promote angiogenesis and cell invasion in Glioblastoma: combination therapies for an effective treatment. Int J Mol Sci 18

    Google Scholar 

  • Kim S, You D, Jeong Y, Yu J, Kim SW, Nam SJ, Lee JE (2018) Berberine down-regulates IL-8 expression through inhibition of the EGFR/MEK/ERK pathway in triple-negative breast cancer cells. Phytomedicine 50:43–49

    Article  CAS  PubMed  Google Scholar 

  • Kim D, Bach DH, Fan Y, Luu TTT, Hong JY, Park HJ, Lee SK (2019) AXL degradation in combination with EGFR-TKI can delay and overcome acquired resistance in human non-small cell lung cancer cells. Cell Death Dis 10:361

    Article  PubMed  PubMed Central  Google Scholar 

  • Koopmans I, Hendriks D, Samplonius DF, van Ginkel RJ, Heskamp S, Wierstra PJ, Bremer E, Helfrich W (2018) A novel bispecific antibody for EGFR-directed blockade of the PD-1/PD-L1 immune checkpoint. Oncoimmunology 7:e1466016

    Article  PubMed  PubMed Central  Google Scholar 

  • Kraemer K, Schmidt U, Fuessel S, Herr A, Wirth MP, Meye A (2006) Microarray analyses in bladder cancer cells: inhibition of hTERT expression down-regulates EGFR. Int J Cancer 119:1276–1284

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Ekavali, Chopra K, Mukherjee M, Pottabathini R, Dhull DK (2015) Current knowledge and pharmacological profile of berberine: an update. Eur J Pharmacol 761:288–297

    Article  CAS  PubMed  Google Scholar 

  • Lee DH, Szczepanski MJ, Lee YJ (2009) Magnolol induces apoptosis via inhibiting the EGFR/PI3K/Akt signaling pathway in human prostate cancer cells. J Cell Biochem 106:1113–1122

    Article  CAS  PubMed  Google Scholar 

  • Lee JY, Lee YM, Chang GC, Yu SL, Hsieh WY, Chen JJ, Chen HW, Yang PC (2011) Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: the versatile adjuvant for gefitinib therapy. PLoS One 6:e23756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Q, Weina P (2010) Artesunate: the best drug in the treatment of severe and complicated malaria. Pharmaceutic (Basel) 3:2322–2332

    Article  CAS  Google Scholar 

  • Li X, Fan XX, Jiang ZB, Loo WT, Yao XJ, Leung EL, Chow LW, Liu L (2017) Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathway. Pharmacol Res 115:45–55

    Article  CAS  PubMed  Google Scholar 

  • Lichtenberger BM, Gerber PA, Holcmann M, Buhren BA, Amberg N, Smolle V, Schrumpf H, Boelke E, Ansari P, Mackenzie C, Wollenberg A, Kislat A, Fischer JW, Rock K, Harder J, Schroder JM, Homey B, Sibilia M (2013) Epidermal EGFR controls cutaneous host defense and prevents inflammation. Sci Transl Med 5:199ra111

    Article  PubMed  CAS  Google Scholar 

  • Lim S-O, Li C-W, Xia W, Lee H-H, Chang S-S, Shen J, Hsu JL, Raftery D, Djukovic D, Gu H, Chang W-C, Wang H-L, Chen M-L, Huo L, Chen C-H, Wu Y, Sahin A, Hanash SM, Hortobagyi GN, Hung M-C (2016) EGFR signaling enhances aerobic glycolysis in triple-negative breast cancer cells to promote tumor growth and immune escape. Cancer Res 76:1284–1296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin H, Zhang C, Zhang H, Xia YZ, Zhang CY, Luo J, Yang L, Kong LY (2018) Physakengose G induces apoptosis via EGFR/mTOR signaling and inhibits autophagic flux in human osteosarcoma cells. Phytomedicine 42:190–198

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Cao W, Zhang B, Liu YQ, Wang ZY, Wu YP, Yu XJ, Zhang XD, Ming PH, Zhou GB, Huang L (2013) The natural compound magnolol inhibits invasion and exhibits potential in human breast cancer therapy. Sci Rep 3:3098

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu X, Feng C, Liu J, Liu J, Li C, Xu C, Niu Y (2018) The importance of EGFR as a biomarker in molecular apocrine breast cancer. Hum Pathol 77:1–10

    Article  PubMed  CAS  Google Scholar 

  • Lizotte PH, Hong RL, Luster TA, Cavanaugh ME, Taus LJ, Wang S, Dhaneshwar A, Mayman N, Yang A, Kulkarni M, Badalucco L, Fitzpatrick E, Kao HF, Kuraguchi M, Bittinger M, Kirschmeier PT, Gray NS, Barbie DA, Janne PA (2018) A high-throughput immune-oncology screen identifies EGFR inhibitors as potent enhancers of antigen-specific cytotoxic T-lymphocyte tumor cell killing. Cancer Immunol Res 6:1511–1523

    Article  PubMed  PubMed Central  Google Scholar 

  • Luo XL, Deng CC, Su XD, Wang F, Chen Z, Wu XP, Liang SB, Liu JH, Fu LW (2018) Loss of MED12 induces tumor dormancy in human epithelial ovarian cancer via downregulation of EGFR. Cancer Res 78:3532–3543

    CAS  PubMed  Google Scholar 

  • Ma H, Yao Q, Zhang AM, Lin S, Wang XX, Wu L, Sun JG, Chen ZT (2011) The effects of artesunate on the expression of EGFR and ABCG2 in A549 human lung cancer cells and a xenograft model. Molecules 16:10556–10569

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma W, Concha-Benavente F, Santegoets S, Welters MJP, Ehsan I, Ferris RL, van der Burg SH (2018) EGFR signaling suppresses type 1 cytokine-induced T-cell attracting chemokine secretion in head and neck cancer. PLoS One 13:e0203402

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mehta R, Katta H, Alimirah F, Patel R, Murillo G, Peng X, Muzzio M, Mehta RG (2013) Deguelin action involves c-met and EGFR signaling pathways in triple negative breast cancer cells. PLoS One 8:e65113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Momcilovic M, Bailey ST, Lee JT, Fishbein MC, Magyar C, Braas D, Graeber T, Jackson NJ, Czernin J, Emberley E, Gross M, Janes J, Mackinnon A, Pan A, Rodriguez M, Works M, Zhang W, Parlati F, Demo S, Garon E, Krysan K, Walser TC, Dubinett SM, Sadeghi S, Christofk HR, Shackelford DB (2017) Targeted inhibition of EGFR and glutaminase induces metabolic crisis in EGFR mutant lung cancer. Cell Rep 18:601–610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nie P, Hu W, Zhang T, Yang Y, Hou B, Zou Z (2015) Synergistic induction of erlotinib-mediated apoptosis by resveratrol in human non-small-cell lung cancer cells by down-regulating survivin and up-regulating PUMA. Cell Physiol Biochem 35:2255–2271

    Article  CAS  PubMed  Google Scholar 

  • Noorafshan A, Ashkani-Esfahani S (2013) A review of therapeutic effects of curcumin. Curr Pharm Des 19:2032–2046

    CAS  PubMed  Google Scholar 

  • Oldrini B, Hsieh WY, Erdjument-Bromage H, Codega P, Carro MS, Curiel-Garcia A, Campos C, Pourmaleki M, Grommes C, Vivanco I, Rohle D, Bielski CM, Taylor BS, Hollmann TJ, Rosenblum M, Tempst P, Blenis J, Squatrito M, Mellinghoff IK (2017) EGFR feedback-inhibition by ran-binding protein 6 is disrupted in cancer. Nat Commun 8:2035

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Park EJ, Min HY, Chung HJ, Hong JY, Kang YJ, Hung TM, Youn UJ, Kim YS, Bae K, Kang SS, Lee SK (2009) Down-regulation of c-Src/EGFR-mediated signaling activation is involved in the honokiol-induced cell cycle arrest and apoptosis in MDA-MB-231 human breast cancer cells. Cancer Lett 277:133–140

    Article  CAS  PubMed  Google Scholar 

  • Park D, Ha IJ, Park SY, Choi M, Lim SL, Kim SH, Lee JH, Ahn KS, Yun M, Lee SG (2016) Morusin induces TRAIL sensitization by regulating EGFR and DR5 in human glioblastoma cells. J Nat Prod 79:317–323

    Article  CAS  PubMed  Google Scholar 

  • Park HJ, Min TR, Chi GY, Choi YH, Park SH (2018) Induction of apoptosis by morusin in human non-small cell lung cancer cells by suppression of EGFR/STAT3 activation. Biochem Biophys Res Comm 505:194–200

    Article  CAS  PubMed  Google Scholar 

  • Postel-Vinay S, Ashworth A (2012) AXL and acquired resistance to EGFR inhibitors. Nat Genet 44:835–836

    Article  CAS  PubMed  Google Scholar 

  • Rasul A, Yu B, Khan M, Zhang K, Iqbal F, Ma T, Yang H (2012) Magnolol, a natural compound, induces apoptosis of SGC-7901 human gastric adenocarcinoma cells via the mitochondrial and PI3K/Akt signaling pathways. Int J Oncol 40:1153–1161

    Article  CAS  PubMed  Google Scholar 

  • Ray K, Ujvari B, Ramana V, Donald J (2018) Cross-talk between EGFR and IL-6 drives oncogenic signaling and offers therapeutic opportunities in cancer. Cytokine Growth Factor Rev 41:18–27

    Article  CAS  PubMed  Google Scholar 

  • Rho JK, Choi YJ, Jeon BS, Choi SJ, Cheon GJ, Woo SK, Kim HR, Kim CH, Choi CM, Lee JC (2010) Combined treatment with silibinin and epidermal growth factor receptor tyrosine kinase inhibitors overcomes drug resistance caused by T790M mutation. Mol Cancer Ther 9:3233–3243

    Article  CAS  PubMed  Google Scholar 

  • Ronellenfitsch MW, Zeiner PS, Mittelbronn M, Urban H, Pietsch T, Reuter D, Senft C, Steinbach JP, Westphal M, Harter PN (2018) Akt and mTORC1 signaling as predictive biomarkers for the EGFR antibody nimotuzumab in glioblastoma. Acta Neuropathol Comm 6:81

    Article  CAS  Google Scholar 

  • Rosner T, Kahle S, Montenegro F, Matlung HL, Jansen JHM, Evers M, Beurskens F, Leusen JHW, Van Den Berg TK, Valerius T (2018) Immune effector functions of human IgG2 antibodies against EGFR. Mol Cancer Ther 18:75–88

    Article  PubMed  Google Scholar 

  • Sarrica A, Kirika N, Romeo M, Salmona M, Diomede L (2018) Safety and toxicology of magnolol and honokiol. Planta Med 84:1151–1164

    Article  CAS  PubMed  Google Scholar 

  • Sasaki T, Hiroki K, Yamashita Y (2013) The role of epidermal growth factor receptor in cancer metastasis and microenvironment. Biomed Res Int 2013:546318

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Savage P, Stebbing J, Bower M, Crook T (2009) Why does cytotoxic chemotherapy cure only some cancers? Nat Clinic Pract Oncol 6:43–52

    Article  CAS  Google Scholar 

  • Serizawa M, Kusuhara M, Zangiacomi V, Urakami K, Watanabe M, Takahashi T, Yamaguchi K, Yamamoto N, Koh Y (2014) Identification of metabolic signatures associated with erlotinib resistance of non-small cell lung cancer cells. Anticancer Res 34:2779–2787

    CAS  PubMed  Google Scholar 

  • Shi X, Wang B (2018) Caught in the “Akt”: cross-talk between EphA2 and EGFR through the Akt-PIKfyve axis maintains cellular sensitivity to EGF. Sci Signal 11:eaau1207

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sibilia M, Kroismayr R, Lichtenberger BM, Natarajan A, Hecking M, Holcmann M (2007) The epidermal growth factor receptor: from development to tumorigenesis. Differentiation 75:770–787

    Article  CAS  PubMed  Google Scholar 

  • Sigismund S, Avanzato D, Lanzetti L (2018) Emerging functions of the EGFR in cancer. Mol Oncol 12:3–20

    Article  PubMed  Google Scholar 

  • Singh T, Gupta NA, Xu S, Prasad R, Velu SE, Katiyar SK (2015) Honokiol inhibits the growth of head and neck squamous cell carcinoma by targeting epidermal growth factor receptor. Oncotarget 6:21268–21282

    PubMed  PubMed Central  Google Scholar 

  • Siu MK, Abou-Kheir W, Yin JJ, Chang Y-S, Barrett B, Suau F, Casey O, Chen W-Y, Fang L, Hynes P, Hsieh Y-Y, Liu Y-N, Huang J, Kelly K (2014) Loss of EGFR signaling-regulated miR-203 promotes prostate cancer bone metastasis and tyrosine kinase inhibitors resistance. Oncotarget 5:3770–3784

    Article  PubMed  PubMed Central  Google Scholar 

  • Skirnisdottir I, Akerud H, Seidal T (2018) Clinical significance of growth factor receptor EGFR and angiogenesis regulator VEGFR2 in patients with ovarian cancer at FIGO stages I-II. Int J Oncol 53:1633–1642

    CAS  PubMed  Google Scholar 

  • Svrcek M, Cosnes J, Tiret E, Bennis M, Parc Y, Flejou JF (2007) Expression of epidermal growth factor receptor (EGFR) is frequent in inflammatory bowel disease (IBD)-associated intestinal cancer. Virchows Arch 450:243–244

    Article  PubMed  Google Scholar 

  • Tang H, Zhang J, Yu Z, Ye L, Li K, Ding F, Feng X, Meng W (2017) Mir-452-3p: a potential tumor promoter that targets the CPEB3/EGFR axis in human hepatocellular carcinoma. Technol Cancer Res Treat 16:1136–1149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Emburgh BO, Sartore-Bianchi A, DI Nicolantonio F, Siena S, Bardelli A (2014) Acquired resistance to EGFR-targeted therapies in colorectal cancer. Mol Oncol 8:1084–1094

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vincent MD, Kuruvilla MS, Leighl NB, Kamel-Reid S (2012) Biomarkers that currently affect clinical practice: EGFR, ALK, MET, KRAS. Curr Oncol 19:S33–S44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Chen S, Xu S, Yu X, Ma D, Hu X, Cao X (2012) In vivo induction of apoptosis by fucoxanthin, a marine carotenoid, associated with down-regulating STAT3/EGFR signaling in sarcoma 180 (S180) xenografts-bearing mice. Mar Drugs 10:2055–2068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Zhu M, Wang L, Chen C, Song Y (2018a) Amphiregulin potentiates airway inflammation and mucus hypersecretion induced by urban particulate matter via the EGFR-PI3Kalpha-AKT/ERK pathway. Cell Signal 53:122–131

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Lai H, Fan X, Luo L, Duan F, Jiang Z, Wang Q, Leung ELH, Liu L, Yao X (2018b) Gossypol inhibits non-small cell lung cancer cells proliferation by targeting EGFR(L858R/T790M). Front Pharmacol 9:728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei Y, Zou Z, Becker N, Anderson M, Sumpter R, Xiao G, Kinch L, Koduru P, Christudass CS, Veltri RW, Grishin NV, Peyton M, Minna J, Bhagat G, Levine B (2013) EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell 154:1269–1284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weihua Z, Tsan R, Huang W-C, Wu Q, Chiu C-H, Fidler IJ, Hung M-C (2008) Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell 13:385–393

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Welcker M, Clurman BE (2014) Oncoprotein ubiquitylation: dimers, degrons, and degradation. Cell Cycle 13:1829–1830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong SF (2005) Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. Clin Therap 27:684–694

    Article  CAS  Google Scholar 

  • Wu SG, Shih JY (2018) Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer 17:38

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xiaoyu W, Linfeng X, Yuanzhi L, Hongmei Z, Hongxi X (2018) Natural products targeting EGFR signaling pathways as potential anticancer drugs. Curr Protein Pept Sci 19:380–388

    Article  CAS  Google Scholar 

  • Yang Z, Ding J, Yang C, Gao Y, Li X, Chen X, Peng Y, Fang J, Xiao S (2012) Immunomodulatory and anti-inflammatory properties of artesunate in experimental colitis. Curr Med Chem 19:4541–4551

    Article  CAS  PubMed  Google Scholar 

  • Yang HK, Chen H, Mao F, Xiao QG, Xie RF, Lei T (2017a) Downregulation of LRIG2 expression inhibits angiogenesis of glioma via EGFR/VEGF-A pathway. Oncol Lett 14:4021–4028

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang Z, Hackshaw A, Feng Q, Fu X, Zhang Y, Mao C, Tang J (2017b) Comparison of gefitinib, erlotinib and afatinib in non-small cell lung cancer: a meta-analysis. Int J Cancer 140:2805–2819

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Shi X, Li C, Wang X, Hou K, Li Z, Zhang X, Fan Y, Qu X, Che X, Liu Y (2018) Long non-coding RNA UCA1 upregulation promotes the migration of hypoxia-resistant gastric cancer cells through the miR-7-5p/EGFR axis. Exp Cell Res 368:194–201

    Article  CAS  PubMed  Google Scholar 

  • Yen CY, Liang SS, Han LY, Chou HL, Chou CK, Lin SR, Chiu CC (2013) Cardiotoxin III inhibits proliferation and migration of oral cancer cells through MAPK and MMP signaling. Sci World J 2013:1–5

    Google Scholar 

  • Yuan XH, Yang J, Wang XY, Zhang XL, Qin TT, Li K (2018) Association between EGFR/KRAS mutation and expression of VEGFA, VEGFR and VEGFR2 in lung adenocarcinoma. Oncol Lett 16:2105–2112

    PubMed  PubMed Central  Google Scholar 

  • Yue J, Lv D, Wang C, Li L, Zhao Q, Chen H, Xu L (2018) Epigenetic silencing of miR-483-3p promotes acquired gefitinib resistance and EMT in EGFR-mutant NSCLC by targeting integrin beta3. Oncogene 37:4300–4312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Han B, Lu H, Zhao Y, Chen X, Meng Q, Cao M, Cai L, Hu J (2018a) USP22 promotes resistance to EGFR-TKIs by preventing ubiquitination-mediated EGFR degradation in EGFR-mutant lung adenocarcinoma. Cancer Lett 433:186–198

    Article  CAS  PubMed  Google Scholar 

  • Zhang HX, Yang JJ, Zhang SA, Zhang SM, Wang JX, Xu ZY, Lin RY (2018b) HIF-1alpha promotes inflammatory response of chronic obstructive pulmonary disease by activating EGFR/PI3K/AKT pathway. Eur Rev Med Pharmacol Sci 22:6077–6084

    PubMed  Google Scholar 

  • Zhang X, Liu G, Ding L, Jiang T, Shao S, Gao Y, Lu Y (2018c) HOXA3 promotes tumor growth of human colon cancer through activating EGFR/Ras/Raf/MEK/ERK signaling pathway. J Cell Biochem 119:2864–2874

    Article  CAS  PubMed  Google Scholar 

  • Zhao Q, Kretschmer N, Bauer R, Efferth T (2015) Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib. Int J Cancer 137:1446–1456

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, He W, Gao X, Li B, Mei C, Xu R, Chen H (2015) Resveratrol overcomes gefitinib resistance by increasing the intracellular gefitinib concentration and triggering apoptosis, autophagy and senescence in PC9/G NSCLC cells. Sci Rep 5:17730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhuang S, Ouedraogo GD, Kochevar IE (2003) Downregulation of epidermal growth factor receptor signaling by singlet oxygen through activation of caspase-3 and protein phosphatases. Oncogene 22:4413–4424

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, South Korea

    Duc-Hiep Bach, Donghwa Kim & Sang Kook Lee

Authors
  1. Duc-Hiep Bach
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donghwa Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sang Kook Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sang Kook Lee .

Editor information

Editors and Affiliations

  1. Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY, USA

    John M. Pezzuto

  2. Department of Science, Systems & Models, Roskilde University, Roskilde, Denmark

    Ole Vang

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bach, DH., Kim, D., Lee, S.K. (2020). Cancer Chemopreventive Potential of Epidermal Growth Factor Receptor Inhibitors from Natural Products. In: Pezzuto, J., Vang, O. (eds) Natural Products for Cancer Chemoprevention. Springer, Cham. https://doi.org/10.1007/978-3-030-39855-2_14

Download citation

Publish with us

Policies and ethics

Search

Navigation