nach oben

Medical Oncology

Erschienen in:

01.07.2023 | Original Paper

Plumbagin binds to epidermal growth factor receptor and mitigate the effects of epidermal growth factor micro-environment in PANC-1 cells

verfasst von: Loganayaki Periyasamy, Bharathi Murugantham, Sridhar Muthusami

Erschienen in: Medical Oncology | Ausgabe 7/2023

Einloggen, um Zugang zu erhalten

Abstract

A sustained increase in the mortality of pancreatic cancer (PC) and sudden metastasis-related mortality is a cause for concern. Aberrant expression of epidermal growth factor (EGF) receptor (EGFR) is noted in several cases of PC metastasis. The present study is aimed at analyzing the expression of EGFR in PC and its relevance to the progression of PC. Despite the number of studies that have shown the benefits of plumbagin on PC cells, its role on cancer stem cells remains largely unknown. To this end, the study used an EGF micro-environment to make cancer stem cells in vitro and ascertained the role of plumbagin in mitigating the actions of EGF. The kaplan–meier (KM) plot indicated reduced overall survival (OS) analysis in PC patients with high EGFR than low EGFR expression. Plumbagin pre-treatment significantly prevented EGF-induced survival, epithelial-to-mesenchymal transition (EMT), clonogenesis, migration, matrix metalloproteinase -2 (MMP-2) gene expression and its secretion, and matrix protein hyaluron production in PANC-1 cells. The computational studies indicate the greater affinity of plumbagin with different domains of EGFR than gefitinib. Several hallmarks of resistance and migration due to EGF are effectively attenuated by plumbagin. Collectively, these results warrant investigating the actions of plumbagin in a pre-clinical study to substantiate these findings.

Galli R, Schmutz-Kober K, Kühnel J, Maak M, Rosenberg R. Pankreaskarzinom [Pancreatic cancer]. Therapeutische Umschau Revue therapeutique. 2021;78(10):605–13. https://doi.org/10.1024/0040-5930/a001317.CrossRefPubMed

Pawlik TM. Pancreatic Cancer. Surg Oncol Clin N Am. 2021;30(4):xiii–xv. https://doi.org/10.1016/j.soc.2021.07.002.CrossRefPubMed

Gaidhani RH, Balasubramaniam G. An epidemiological review of pancreatic cancer with special reference to India. Indian J Med Sci. 2021;73(1):99–109. https://doi.org/10.25259/IJMS_92_2020.CrossRef

Shrikhande SV, Barreto S, Sirohi B, Bal M, Shrimali RK, Chacko RT, Rath GK. Indian council of medical research consensus document for the management of pancreatic cancer. Indian J Med Paediat Oncol. 2019;40(01):9–14. https://doi.org/10.4103/ijmpo.ijmpo_29_19.CrossRef

Muthusami S, Prabakaran DS, Yu JR, Park WY. EGF-induced expression of Fused Toes Homolog (FTS) facilitates epithelial-mesenchymal transition and promotes cell migration in ME180 cervical cancer cells. Cancer Lett. 2014;351(2):252–9. https://doi.org/10.1016/j.canlet.2014.06.007.CrossRefPubMed

Xelwa N, Candy GP, Devar J, Omoshoro-Jones J, Smith M, Nweke EE. Targeting growth factor signaling pathways in pancreatic cancer: towards inhibiting chemoresistance. Frontiers Oncol. 2021;11:683788. https://doi.org/10.3389/fonc.2021.683788.CrossRef

Xu Z, Zhang Y, Jiang J, Yang Y, Shi R, Hao B, Zhang Z, Huang Z, Kim JW, Zhang G. Epidermal growth factor induces HCCR expression via PI3K/Akt/mTOR signaling in PANC-1 pancreatic cancer cells. BMC Cancer. 2010;10:161. https://doi.org/10.1186/1471-2407-10-161.CrossRefPubMedPubMedCentral

Fitzgerald TL, Lertpiriyapong K, Cocco L, Martelli AM, Libra M, Candido S, Montalto G, Cervello M, Steelman L, Abrams SL, McCubrey JA. Roles of EGFR and KRAS and their downstream signaling pathways in pancreatic cancer and pancreatic cancer stem cells. Adv Bioll Regul. 2015;59:65–81. https://doi.org/10.1016/j.jbior.2015.06.003.CrossRef

Park SJ, Gu MJ, Lee DS, Yun SS, Kim HJ, Choi JH. EGFR expression in pancreatic intraepithelial neoplasia and ductal adenocarcinoma. Int J Clin Exp Pathol. 2015;8(7):8298–304.PubMedPubMedCentral

10.

Uribe ML, Marrocco I, Yarden Y. EGFR in cancer: signaling mechanisms, drugs, and acquired resistance. Cancers. 2021;13(11):2748. https://doi.org/10.3390/cancers13112748.CrossRefPubMedPubMedCentral

11.

Periyasamy L, Muruganantham B, Deivasigamani M, Lakshmanan H, Muthusami S. Acetogenin extracted from annona muricata prevented the actions of EGF in PA-1 ovarian cancer cells. Protein Pept Lett. 2021;28(3):304–14. https://doi.org/10.2174/0929866527666200916141730.CrossRefPubMed

12.

Muthusami S, Sabanayagam R, Periyasamy L, Muruganantham B, Park WY. A review on the role of epidermal growth factor signaling in the development, progression, and treatment of cervical cancer. Int J Biol Macromol. 2022;194:179–87. https://doi.org/10.1016/j.ijbiomac.2021.11.117.CrossRefPubMed

13.

Valsecchi ME, McDonald M, Brody JR, Hyslop T, Freydin B, Yeo CJ, Solomides C, Peiper SC, Witkiewicz AK. Epidermal growth factor receptor and insulinlike growth factor 1 receptor expression predict poor survival in pancreatic ductal adenocarcinoma. Cancer. 2012;118(14):3484–93. https://doi.org/10.1002/cncr.26661.CrossRefPubMed

14.

Nedaeinia R, Avan A, Manian M, Salehi R, Ghayour-Mobarhan M. EGFR as a potential target for the treatment of pancreatic cancer: dilemma and controversies. Curr Drug Targets. 2014;15(14):1293–301. https://doi.org/10.2174/1389450115666141125123003.CrossRefPubMed

15.

Yang ZY, Yuan JQ, Di MY, Zheng DY, Chen JZ, Ding H, Wu XY, Huang YF, Mao C, Tang JL. Gemcitabine plus erlotinib for advanced pancreatic cancer: a systematic review with meta-analysis. PLoS ONE. 2013;8(3):e57528d. https://doi.org/10.1371/journal.pone.0057528.CrossRef

16.

Periyasamy L, Muruganantham B, Park WY, Muthusami S. Phyto-targeting the CEMIP expression as a strategy to prevent pancreatic cancer metastasis. Curr Pharm Des. 2022;28(11):922–46. https://doi.org/10.2174/1381612828666220302153201.CrossRefPubMed

17.

Periyasamy L, Murugantham B, Sundararaj R, Krishnamoorthy S, Muthusami S. Screening of MMP-2 inhibiting phytoconstituents for the development of newer pancreatic cancer modalities. Protein Pept Lett. 2023; 30(4):304-313. https://doi.org/10.2174/0929866530666230213113835.CrossRefPubMed

18.

Hafeez BB, Jamal MS, Fischer JW, Mustafa A, Verma AK. Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF-κB signaling pathways. Int J Cancer. 2012;131(9):2175–86. https://doi.org/10.1002/ijc.27478.CrossRefPubMedPubMedCentral

19.

Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47(W1):W556–60. https://doi.org/10.1093/nar/gkz430.CrossRefPubMedPubMedCentral

20.

Rappé AK, Casewit CJ, Colwell KS, Goddard WA III, Skiff WM. UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations. J Am Chem Soc. 1992;114(25):10024–35. https://doi.org/10.1021/ja00051a040.CrossRef

21.

Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455–61. https://doi.org/10.1002/jcc.21334.CrossRefPubMedPubMedCentral

22.

Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Meth Mol Biol. 2015;1263:243–50. https://doi.org/10.1007/978-1-4939-2269-7_19.CrossRef

23.

Sohal DP, Mangu PB, Laheru D. Metastatic pancreatic cancer: american society of clinical oncology clinical practice guideline summary. J Oncol Pract. 2017;13(4):261–4. https://doi.org/10.1200/JOP.2016.017368.CrossRefPubMed

24.

Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol. 2019;10(1):10–27. https://doi.org/10.14740/wjon1166.CrossRefPubMedPubMedCentral

25.

Macchini M, Chiaravalli M, Zanon S, Peretti U, Mazza E, Gianni L, Reni M. Chemotherapy in elderly patients with pancreatic cancer: Efficacy, feasibility and future perspectives. Cancer Treat Rev. 2019;72:1–6. https://doi.org/10.1016/j.ctrv.2018.10.013.CrossRefPubMed

26.

Liu H, Zhang B, Sun Z. Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan-cancer analysis. Cancer commun. 2020;40(1):43–59. https://doi.org/10.1002/cac2.12005.CrossRef

27.

Pandey K, Tripathi SK, Panda M, Biswal BK. Prooxidative activity of plumbagin induces apoptosis in human pancreatic ductal adenocarcinoma cells via intrinsic apoptotic pathway. Toxicol in vitro Int J published Assoc. 2020;65:104788. https://doi.org/10.1016/j.tiv.2020.104788.CrossRef

28.

Wang F, Wang Q, Zhou ZW, Yu SN, Pan ST, He ZX, Zhang X, Wang D, Yang YX, Yang T, Sun T, Li M, Qiu JX, Zhou SF. Plumbagin induces cell cycle arrest and autophagy and suppresses epithelial to mesenchymal transition involving PI3K/Akt/mTOR-mediated pathway in human pancreatic cancer cells. Drug Des Dev Ther. 2015;9:537–60. https://doi.org/10.2147/DDDT.S73689.CrossRef

29.

Binker MG, Binker-Cosen AA, Richards D, Oliver B, Cosen-Binker LI. EGF promotes invasion by PANC-1 cells through Rac1/ROS-dependent secretion and activation of MMP-2. Biochem Biophys Res Commun. 2009;379(2):445–50. https://doi.org/10.1016/j.bbrc.2008.12.080.CrossRefPubMed

30.

Liu W, Wang K, Gong K, Li X, Luo K. Epidermal growth factor enhances MPC-83 pancreatic cancer cell migration through the upregulation of aquaporin 3. Mol Med Rep. 2012;6(3):607–10. https://doi.org/10.3892/mmr.2012.966.CrossRefPubMed

31.

Taddei ML, Giannoni E, Fiaschi T, Chiarugi P. Anoikis: an emerging hallmark in health and diseases. J Pathol. 2012;226(2):380–93. https://doi.org/10.1002/path.3000.CrossRefPubMed

32.

Li J, Kleeff J, Giese N, Büchler MW, Korc M, Friess H. Gefitinib (“Iressa”, ZD1839), a selective epidermal growth factor receptor tyrosine kinase inhibitor, inhibits pancreatic cancer cell growth, invasion, and colony formation. Int J Oncol. 2004;25(1):203–10.PubMed

33.

Tahkola K, Ahtiainen M, Mecklin JP, Kellokumpu I, Laukkarinen J, Tammi M, Tammi R, Väyrynen JP, Böhm J. Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer. Sci Rep. 2021;11(1):12216. https://doi.org/10.1038/s41598-021-91796-x.CrossRefPubMedPubMedCentral

34.

Seufferlein T, Ducreux M, Hidalgo M, Prager G, Van Cutsem E. More than a gel-Hyaluronic acid, a central component in the microenvironment of pancreatic cancer. Eur Oncol Haematol. 2018;14(1):40–4. https://doi.org/10.17925/EOH.2018.14.1.40.CrossRef

35.

Roy R, Mandal S, Chakrabarti J, Saha P, Panda CK. Downregulation of Hyaluronic acid-CD44 signaling pathway in cervical cancer cell by natural polyphenols Plumbagin, Pongapin and Karanjin. Mol Cell Biochem. 2021;476(10):3701–9. https://doi.org/10.1007/s11010-021-04195-1.CrossRefPubMed

Titel: Plumbagin binds to epidermal growth factor receptor and mitigate the effects of epidermal growth factor micro-environment in PANC-1 cells
verfasst von: Loganayaki Periyasamy
Bharathi Murugantham
Sridhar Muthusami
Publikationsdatum: 01.07.2023
Verlag: Springer US
Erschienen in: Medical Oncology / Ausgabe 7/2023
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-023-02048-z

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Plumbagin binds to epidermal growth factor receptor and mitigate the effects of epidermal growth factor micro-environment in PANC-1 cells

Abstract

Neu im Fachgebiet Onkologie

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Perioperative Checkpointhemmer-Therapie verbessert NSCLC-Prognose

Positiver FIT: Die Ursache liegt nicht immer im Dickdarm

Update Onkologie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2023

Depletion of enhancer zeste homolog 2 (EZH2) directs transcription factors associated with T cell differentiation through epigenetic regulation of Yin Yang 1(YY1) in combating non-small cell lung cancer (NSCLC)

Current advances in microbial-based cancer therapies

In vitro chemo-preventive efficacy of synthetic progestin Norethindrone in human epithelial ovarian cancer

Efficacy and safety of EGFR inhibitor gefitinib in recurrent or metastatic cervical cancer: a preliminary report

The future of cancer immunotherapy: DNA vaccines leading the way

Therapeutic targeting approach on epithelial-mesenchymal plasticity to combat cancer metastasis

Neu im Fachgebiet Onkologie

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Perioperative Checkpointhemmer-Therapie verbessert NSCLC-Prognose

Positiver FIT: Die Ursache liegt nicht immer im Dickdarm

Update Onkologie