In-silico Molecular Docking of Indigofera Tinctoria Phytocompounds to Target EGFR/ERK and FGFR/FGF Pathway Proteins Involved in Prostate Cancer

[{“box”:0,”content”:”

n

Home

n

 > 

n

ijmbr

n

 > 

n

Original Research

n

Views: 606

n

n

n

n

n

By [foreach 286]u00a0

u00a0Nidhi Premanand Honavar,

[/foreach]
nApril 24, 2023 at 9:19 am

n

nAbstract

n

Objective: Prostate cancer being the second major cause of cancer related deaths in males, affects the small walnut shaped gland below the bladder called Prostate gland. The epidermal growth factor protein (EGFR), cascade protein (ERK) and the Fibroblast Growth Factor Proteins (FGFR and FGF) are involved in the different signalling pathways which leads to the formation of different products, that are responsible for the progression of the cancer and thus can be considered as the therapeutic targets. Indigofera tinctoria, a medicinal plant with proven anti-cancerous properties, was chosen for this study to investigate its different compound’s therapeutic effect against the target proteins, which are responsible for the Prostate cancer. Methods: In this study, 20 different compounds were selected from the Indigofera tinctoria plant as ligands to check for their binding affinity against the Target proteins (EGFR, ERK, FGFR and FGF). The docking of the ligands with the target proteins were done by using PyRx Virtual tool. The computational investigation of all the ligands and the target proteins, such as its molecular structure, phytochemistry, their therapeutic actions and other data was carried out. The protein structure validation and the pharmacological evaluation of the ligands were done using the BIOVIA Discovery studio, PDB sum generate and ADMET lab 2.0 respectively. Result: The results of this study showed that the compounds, Pseudosemiglabrin, [(12S,15R,16R)-14,14-dimethyl-6-oxo-4-phenyl-3,11,13-trioxatetracyclo [8.6.0.02,7.012,16] hexadeca-1(10),2(7),4,8-tetraen-15-yl] acetate, Deguelin, Sumatrol and Rotenone showed good binding affinity with the target proteins and can be considered as a potential drug for the prostate cancer. Conclusion: The compounds selected were found to be active against the target proteins for the prostate cancer and thus can be utilised for the cancer suppression. The further invitro studies need to be done to support this study.

n

n

n

n

Volume :u00a0u00a01 | Issue :u00a0u00a01 | Received :u00a0u00a0March 2, 2023 | Accepted :u00a0u00a0April 2, 2023 | Published :u00a0u00a0April 18, 2023n[if 424 equals=”Regular Issue”][This article belongs to International Journal of Molecular Biotechnological Research(ijmbr)] [/if 424][if 424 equals=”Special Issue”][This article belongs to Special Issue In-silico Molecular Docking of Indigofera Tinctoria Phytocompounds to Target EGFR/ERK and FGFR/FGF Pathway Proteins Involved in Prostate Cancer under section in International Journal of Molecular Biotechnological Research(ijmbr)] [/if 424]
Keywords Prostate cancer, Molecular docking, Indigofera tinctoria, Epidermal Growth Factor Receptors, Fibroblast Growth Factor Receptors, extracellular-regulated kinase, ADMET lab 2.0,

n

n

n

n

n

n[if 992 equals=”Transformative”]

n

n

Full Text

n

n

n

[/if 992][if 992 not_equal=”Transformative”]

n

n

Full Text

n

n

n

[/if 992] n

nn

[if 379 not_equal=””]n

[foreach 379]n

n[/foreach]

n[/if 379]

n

References

n[if 1104 equals=””]n

  1. Rawla, P. (2019). Epidemiology of prostate cancer. World journal of oncology, 10(2), 63.
  2. Xie, Y., Su, N., Yang, J. et al. FGF/FGFR signaling in health and disease. Sig Transduct Target Ther 5, 181 (2020). https://doi.org/10.1038/s41392-020-00222-7
  3. Normanno, N., De Luca, A., Bianco, C., Strizzi, L., Mancino, M., Maiello, M. R., Carotenuto, A., De Feo, G., Caponigro, F., & Salomon, D. S. (2006). Epidermal growth factor receptor (EGFR) signaling in cancer. Gene, 366(1), 2–16. https://doi.org/10.1016/j.gene.2005.10.018
  4. Uribe, M. L., Marrocco, I., & Yarden, Y. (2021). EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance. Cancers, 13(11), 2748. https://doi.org/10.3390/cancers13112748
  5. Giacomini, A., Grillo, E., Rezzola, S., Ribatti, D., Rusnati, M., Ronca, R., & Presta, M. (2021). The FGF/FGFR system in the physiopathology of the prostate gland. Physiological Reviews, 101(2), 569–610.
  6. Chen, K. L., Chang, W. S. W., Cheung, C. H. A., Lin, C. C., Huang, C. C., Yang, Y. N., … & Chang, J. Y. (2012). Targeting cathepsin S induces tumor cell autophagy via the EGFR–ERK signaling pathway. Cancer letters, 317(1), 89–98.

 

  1. Itoh, N., & Ornitz, D. M. (2004). Evolution of the Fgf and Fgfr gene families. TRENDS in Genetics, 20(11), 563–569.
  2. Lu, Y., Liu, B., Liu, Y., Yu, X., & Cheng, G. (2020). Dual effects of active ERK in cancer: A potential target for enhancing radiosensitivity. Oncology letters, 20(2), 993–1000. https://doi.org/10.3892/ol.2020.11684

 

 

  1. Motamarri, N. S., Karthikeyan, M., Rajasekar, S., & Gopal, V. (2012). Indigofera tinctoria Linn-a phytopharmacological review. International Journal of Research in Pharmaceutical and Biomedical Sciences, 3(1), 164–169.
  2. Thamilselvan, V., Menon, M., & Thamilselvan, S. (2011). Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 β/β-catenin pathway. International journal of cancer, 129(12), 2916–2927. https://doi.org/10.1002/ijc.25949
  3. Ahmed Hassan, L. E., Khadeer Ahamed, M. B., Abdul Majid, A. S., Iqbal, M. A., Al Suede, F. S., Haque, R. A., Ismail, Z., Ein, O. C., & Majid, A. M. (2014). Crystal structure elucidation and anticancer studies of (-)-pseudosemiglabrin: a flavanone isolated from the aerial parts of Tephrosia apollinea. PloS one, 9(6), e90806. https://doi.org/10.1371/journal.pone.0090806
  4. Gerhäuser, C., Mar, W., Lee, S. K., Suh, N., Luo, Y., Kosmeder, J., … & Pezzuto, J. M. (1995). Rotenoids mediate potent cancer chemopreventive activity through transcriptional regulation of ornithine decarboxylase. Nature medicine, 1(3), 260–266.
  5. Wei, Y. F., Su, J., Deng, Z. L., Zhu, C., Yuan, L., Lu, Z. J., & Zhu, Q. Y. (2015). Zhonghua nan ke xue = National journal of andrology, 21(9), 788–791.
  6. Choi, S., Choi, Y., Dat, N. T., Hwangbo, C., Lee, J. J., & Lee, J. H. (2010). Tephrosin induces internalization and degradation of EGFR and ErbB2 in HT-29 human colon cancer cells. Cancer letters, 293(1), 23–30. https://doi.org/10.1016/j.canlet.2009.12.012
  7. Da, J., Xu, M., Wang, Y., Li, W., Lu, M., & Wang, Z. (2019). Kaempferol Promotes Apoptosis While Inhibiting Cell Proliferation via Androgen-Dependent Pathway and Suppressing Vasculogenic Mimicry and Invasion in Prostate Cancer. Analytical cellular pathology (Amsterdam), 2019, 1907698. https://doi.org/10.1155/2019/1907698

 

 

  1. Orton, R. J., Adriaens, M. E., Gormand, A., Sturm, O. E., Kolch, W., & Gilbert, D. R. (2009). Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway. BMC systems biology, 3(1), 1–17.

 

 

  1. Renukadevi, K. P., & Sultana, S. S. (2011). Determination of antibacterial, antioxidant and cytotoxicity effect of Indigofera tinctoria on lung cancer cell line NCI-h69. Int J Pharmacol, 7(3), 356–362.
  2. Srinivasan, N. (2018). Medicinal plants for cancer treatment: A review approach. International Journal of Biology Research, 3(4), 57-61.
  3. Szymczyk, J., Sluzalska, K. D., Materla, I., Opalinski, L., Otlewski, J., & Zakrzewska, M. (2021). FGF/FGFR-dependent molecular mechanisms underlying anti-cancer drug resistance. Cancers, 13(22), 5796.
  4. Xiong, G., Wu, Z., Yi, J., Fu, L., Yang, Z., Hsieh, C., … & Cao, D. (2021). ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Research, 49(W1), W5–W14.
  5. Pienta, K. J., & Esper, P. S. (1993). Risk factors for prostate cancer. Annals of internal medicine, 118(10), 793–803.
  6. Crawford, E. D. (2003). Epidemiology of prostate cancer. Urology, 62(6), 3–12.

 

  1. Litwin, M. S., & Tan, H. J. (2017). The diagnosis and treatment of prostate cancer: a review. Jama, 317(24), 2532–2542.

 

 

  1. Pernar, C. H., Ebot, E. M., Wilson, K. M., & Mucci, L. A. (2018). The epidemiology of prostate cancer. Cold Spring Harbor perspectives in medicine, 8(12), a030361.

nn[/if 1104] [if 1104 not_equal=””]n

    [foreach 1102]n t

  1. [if 1106 equals=””], [/if 1106][if 1106 not_equal=””], [/if 1106]

    2. n[/foreach]

n[/if 1104]

n[if 1114 equals=”Yes”]n

n[/if 1114]

n function myFunction2() {n var x = document.getElementById(“browsefigure”);n if (x.style.display === “block”) {n x.style.display = “none”;n }n else {n x.style.display = “Block”;n }n }n document.querySelector(“.prevBtn”).addEventListener(“click”, () => {n changeSlides(-1);n });n document.querySelector(“.nextBtn”).addEventListener(“click”, () => {n changeSlides(1);n });n var slideIndex = 1;n showSlides(slideIndex);n function changeSlides(n) {n showSlides((slideIndex += n));n }n function currentSlide(n) {n showSlides((slideIndex = n));n }n function showSlides(n) {n var i;n var slides = document.getElementsByClassName(“Slide”);n var dots = document.getElementsByClassName(“Navdot”);n if (n > slides.length) {n slideIndex = 1;n }n if (n (item.style.display = “none”));n Array.from(dots).forEach(n item => (item.className = item.className.replace(” selected”, “”))n );n slides[slideIndex – 1].style.display = “block”;n dots[slideIndex – 1].className += ” selected”;n }n

n

n

[if 424 not_equal=”Regular Issue”] Regular Issue[/if 424] Transformative Original Research

n

International Journal of Molecular Biotechnological Research Cover

International Journal of Molecular Biotechnological Research

Editors Overview

ijmbr maintains an Editorial Board of practicing researchers from around the world, to ensure manuscripts are handled by editors who are experts in the field of study.

n

“},{“box”:4,”content”:”

nnfunction myFunction2() {nvar x = document.getElementById(“browsefigure”);nif (x.style.display === “block”) {nx.style.display = “none”;}nelse {x.style.display = “Block”;}}ndocument.querySelector(“.prevBtn”).addEventListener(“click”, () => {nchangeSlides(-1);});ndocument.querySelector(“.nextBtn”).addEventListener(“click”, () => {nchangeSlides(1);});nvar slideIndex = 1;nshowSlides(slideIndex);nfunction changeSlides(n) {nshowSlides((slideIndex += n));}nfunction currentSlide(n) {nshowSlides((slideIndex = n));}nfunction showSlides(n) {nvar i;nvar slides = document.getElementsByClassName(“Slide”);nvar dots = document.getElementsByClassName(“Navdot”);nif (n > slides.length) {slideIndex = 1;}nif (n (item.style.display = “none”));nArray.from(dots).forEach(nitem => (item.className = item.className.replace(” selected”, “”))n);nslides[slideIndex – 1].style.display = “block”;ndots[slideIndex – 1].className += ” selected”;n}”},{“box”:1,”content”:”

    By  [foreach 286]n

  1. n

    Nidhi Premanand Honavar

    n

    2. [/foreach]

n

    [foreach 286] [if 1175 not_equal=””]n t

  1. Student,Department of Biotechnology, Indian Academy Degree College Autonomous, Hennur,Bangalore, Karnataka,India

    2. n[/if 1175][/foreach]

n

n

n

n

n

Abstract

nObjective: Prostate cancer being the second major cause of cancer related deaths in males, affects the small walnut shaped gland below the bladder called Prostate gland. The epidermal growth factor protein (EGFR), cascade protein (ERK) and the Fibroblast Growth Factor Proteins (FGFR and FGF) are involved in the different signalling pathways which leads to the formation of different products, that are responsible for the progression of the cancer and thus can be considered as the therapeutic targets. Indigofera tinctoria, a medicinal plant with proven anti-cancerous properties, was chosen for this study to investigate its different compound’s therapeutic effect against the target proteins, which are responsible for the Prostate cancer. Methods: In this study, 20 different compounds were selected from the Indigofera tinctoria plant as ligands to check for their binding affinity against the Target proteins (EGFR, ERK, FGFR and FGF). The docking of the ligands with the target proteins were done by using PyRx Virtual tool. The computational investigation of all the ligands and the target proteins, such as its molecular structure, phytochemistry, their therapeutic actions and other data was carried out. The protein structure validation and the pharmacological evaluation of the ligands were done using the BIOVIA Discovery studio, PDB sum generate and ADMET lab 2.0 respectively. Result: The results of this study showed that the compounds, Pseudosemiglabrin, [(12S,15R,16R)-14,14-dimethyl-6-oxo-4-phenyl-3,11,13-trioxatetracyclo [8.6.0.02,7.012,16] hexadeca-1(10),2(7),4,8-tetraen-15-yl] acetate, Deguelin, Sumatrol and Rotenone showed good binding affinity with the target proteins and can be considered as a potential drug for the prostate cancer. Conclusion: The compounds selected were found to be active against the target proteins for the prostate cancer and thus can be utilised for the cancer suppression. The further invitro studies need to be done to support this study.n

n

n

Keywords: Prostate cancer, Molecular docking, Indigofera tinctoria, Epidermal Growth Factor Receptors, Fibroblast Growth Factor Receptors, extracellular-regulated kinase, ADMET lab 2.0,

n[if 424 equals=”Regular Issue”][This article belongs to International Journal of Molecular Biotechnological Research(ijmbr)]

n[/if 424][if 424 equals=”Special Issue”][This article belongs to Special Issue under section in International Journal of Molecular Biotechnological Research(ijmbr)] [/if 424]

n

n

n

n[if 992 equals=”Transformative”]n

n

n

Full Text

n

n

nn[/if 992]n[if 992 not_equal=”Transformative”]n

n

Full Text

n

n

n

https://storage.googleapis.com/journals-stmjournals-com-wp-media-to-gcp-offload/2023/04/89a17e01-28-40-in-silico-molecular-docking-of-indigofera-tinctoria-phytocompounds-to-target-egfr.pdf

n

[/if 992]n[if 379 not_equal=””]

Browse Figures

n

n

[foreach 379]n

n[/foreach]

n

[/if 379]n

n

References

n[if 1104 equals=””]

  1. Rawla, P. (2019). Epidemiology of prostate cancer. World journal of oncology, 10(2), 63.
  2. Xie, Y., Su, N., Yang, J. et al. FGF/FGFR signaling in health and disease. Sig Transduct Target Ther 5, 181 (2020). https://doi.org/10.1038/s41392-020-00222-7
  3. Normanno, N., De Luca, A., Bianco, C., Strizzi, L., Mancino, M., Maiello, M. R., Carotenuto, A., De Feo, G., Caponigro, F., & Salomon, D. S. (2006). Epidermal growth factor receptor (EGFR) signaling in cancer. Gene, 366(1), 2–16. https://doi.org/10.1016/j.gene.2005.10.018
  4. Uribe, M. L., Marrocco, I., & Yarden, Y. (2021). EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance. Cancers, 13(11), 2748. https://doi.org/10.3390/cancers13112748
  5. Giacomini, A., Grillo, E., Rezzola, S., Ribatti, D., Rusnati, M., Ronca, R., & Presta, M. (2021). The FGF/FGFR system in the physiopathology of the prostate gland. Physiological Reviews, 101(2), 569–610.
  6. Chen, K. L., Chang, W. S. W., Cheung, C. H. A., Lin, C. C., Huang, C. C., Yang, Y. N., … & Chang, J. Y. (2012). Targeting cathepsin S induces tumor cell autophagy via the EGFR–ERK signaling pathway. Cancer letters, 317(1), 89–98.

 

  1. Itoh, N., & Ornitz, D. M. (2004). Evolution of the Fgf and Fgfr gene families. TRENDS in Genetics, 20(11), 563–569.
  2. Lu, Y., Liu, B., Liu, Y., Yu, X., & Cheng, G. (2020). Dual effects of active ERK in cancer: A potential target for enhancing radiosensitivity. Oncology letters, 20(2), 993–1000. https://doi.org/10.3892/ol.2020.11684

 

 

  1. Motamarri, N. S., Karthikeyan, M., Rajasekar, S., & Gopal, V. (2012). Indigofera tinctoria Linn-a phytopharmacological review. International Journal of Research in Pharmaceutical and Biomedical Sciences, 3(1), 164–169.
  2. Thamilselvan, V., Menon, M., & Thamilselvan, S. (2011). Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 β/β-catenin pathway. International journal of cancer, 129(12), 2916–2927. https://doi.org/10.1002/ijc.25949
  3. Ahmed Hassan, L. E., Khadeer Ahamed, M. B., Abdul Majid, A. S., Iqbal, M. A., Al Suede, F. S., Haque, R. A., Ismail, Z., Ein, O. C., & Majid, A. M. (2014). Crystal structure elucidation and anticancer studies of (-)-pseudosemiglabrin: a flavanone isolated from the aerial parts of Tephrosia apollinea. PloS one, 9(6), e90806. https://doi.org/10.1371/journal.pone.0090806
  4. Gerhäuser, C., Mar, W., Lee, S. K., Suh, N., Luo, Y., Kosmeder, J., … & Pezzuto, J. M. (1995). Rotenoids mediate potent cancer chemopreventive activity through transcriptional regulation of ornithine decarboxylase. Nature medicine, 1(3), 260–266.
  5. Wei, Y. F., Su, J., Deng, Z. L., Zhu, C., Yuan, L., Lu, Z. J., & Zhu, Q. Y. (2015). Zhonghua nan ke xue = National journal of andrology, 21(9), 788–791.
  6. Choi, S., Choi, Y., Dat, N. T., Hwangbo, C., Lee, J. J., & Lee, J. H. (2010). Tephrosin induces internalization and degradation of EGFR and ErbB2 in HT-29 human colon cancer cells. Cancer letters, 293(1), 23–30. https://doi.org/10.1016/j.canlet.2009.12.012
  7. Da, J., Xu, M., Wang, Y., Li, W., Lu, M., & Wang, Z. (2019). Kaempferol Promotes Apoptosis While Inhibiting Cell Proliferation via Androgen-Dependent Pathway and Suppressing Vasculogenic Mimicry and Invasion in Prostate Cancer. Analytical cellular pathology (Amsterdam), 2019, 1907698. https://doi.org/10.1155/2019/1907698

 

 

  1. Orton, R. J., Adriaens, M. E., Gormand, A., Sturm, O. E., Kolch, W., & Gilbert, D. R. (2009). Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway. BMC systems biology, 3(1), 1–17.

 

 

  1. Renukadevi, K. P., & Sultana, S. S. (2011). Determination of antibacterial, antioxidant and cytotoxicity effect of Indigofera tinctoria on lung cancer cell line NCI-h69. Int J Pharmacol, 7(3), 356–362.
  2. Srinivasan, N. (2018). Medicinal plants for cancer treatment: A review approach. International Journal of Biology Research, 3(4), 57-61.
  3. Szymczyk, J., Sluzalska, K. D., Materla, I., Opalinski, L., Otlewski, J., & Zakrzewska, M. (2021). FGF/FGFR-dependent molecular mechanisms underlying anti-cancer drug resistance. Cancers, 13(22), 5796.
  4. Xiong, G., Wu, Z., Yi, J., Fu, L., Yang, Z., Hsieh, C., … & Cao, D. (2021). ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Research, 49(W1), W5–W14.
  5. Pienta, K. J., & Esper, P. S. (1993). Risk factors for prostate cancer. Annals of internal medicine, 118(10), 793–803.
  6. Crawford, E. D. (2003). Epidemiology of prostate cancer. Urology, 62(6), 3–12.

 

  1. Litwin, M. S., & Tan, H. J. (2017). The diagnosis and treatment of prostate cancer: a review. Jama, 317(24), 2532–2542.

 

 

  1. Pernar, C. H., Ebot, E. M., Wilson, K. M., & Mucci, L. A. (2018). The epidemiology of prostate cancer. Cold Spring Harbor perspectives in medicine, 8(12), a030361.

n[/if 1104][if 1104 not_equal=””]n

    [foreach 1102]n t

  1. [if 1106 equals=””], [/if 1106][if 1106 not_equal=””],[/if 1106]

    2. n[/foreach]

n[/if 1104]

n

n[if 1114 equals=”Yes”]n

n[/if 1114]”},{“box”:2,”content”:”

Regular Issue Transformative Original Research

n

n

n

n

n

International Journal of Molecular Biotechnological Research

n

[if 344 not_equal=””]ISSN: [/if 344]

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

n

Volume 1
Issue 1
Received March 2, 2023
Accepted April 2, 2023
Published April 18, 2023

n

n

Views: 606

n

n

Editor

n

n [foreach 1188] n

[if 1193 equals=””][else][/if] 

n [/foreach]n

n

n

Reviewer

n

n [foreach 1176] n

[if 1181 equals=””][else][/if] 

n [/foreach]n

n

n n function myfun() {n x=document.getElementById(“editor”);n y=document.getElementById(“down”);n z=document.getElementById(“up”);n if(x.style.display==”none”){n x.style.display=”block”;n }n else {n x.style.display=”none”;n }n if(y.style.display==”none”){n y.style.display=”block”;n }n else {n y.style.display=”none”;n }n if(z.style.display==”none”){n z.style.display=”block”;n }n else {n z.style.display=”none”;n }n }n function myfun2() {n x=document.getElementById(“reviewer”);n y=document.getElementById(“down2”);n z=document.getElementById(“up2″);n if(x.style.display==”none”){n x.style.display=”block”;n }n else {n x.style.display=”none”;n }n if(y.style.display==”none”){n y.style.display=”block”;n }n else {n y.style.display=”none”;n }n if(z.style.display==”none”){n z.style.display=”block”;n }n else {n z.style.display=”none”;n }n }n n

n”},{“box”:6,”content”:”“}]