Screening and in vitro Biological Evaluation of Novel Multiple Tyrosine Kinases Inhibitors as Promising Anticancer Agents


如何引用文章

全文:

详细

Background:Tyrosine kinases have emerged as key stimulatory drivers in several cancer-related pathways. This is particularly evident in non-small cell lung cancer with regulating cell growth and apoptosis and so on. Tyrosine kinase inhibitors (TKI) are one breakthrough option that could improve the life quality of cancer patients.

Objective:This study aims to find more effective tyrosine kinase inhibitors.

Methods:In this study, natural products from TargetMol that may be the potential TKI for lung cancer were screened through structure-based virtual screening and experimental validation. Moreover, the binding between the hit compounds and tyrosine kinase was explored.

Results:From the study findings, Gramicidin and Tannic acid have strong interactions with the four tyrosine kinases (ALK, TRK, MET, and ABL), and this could significantly inhibit the viability of A549 cells in a concentrationdependent manner.

Conclusion:These findings indicated that Gramicidin and Tannic acid might be potential multiple TKI and are promising anticancer agents that call for further study.

作者简介

Xiuying Li

Pulmonary and Critical Care Medicine,The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People 's Hospital

Email: info@benthamscience.net

Pinglang Ruan

Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital of Central South University

Email: info@benthamscience.net

Gang Jiang

Pulmonary and Critical Care Medicine,The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People 's Hospital

Email: info@benthamscience.net

Weidong Zhang

Pulmonary and Critical Care Medicine,The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People 's Hospital

编辑信件的主要联系方式.
Email: info@benthamscience.net

参考

  1. World Health Organization. Cancer, 2022. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer
  2. Vinod, S.K.; Hau, E. Radiotherapy treatment for lung cancer: Current status and future directions. Respirology, 2020, 25(S2), 61-71. doi: 10.1111/resp.13870 PMID: 32516852
  3. Ettinger, D.S.; Wood, D.E.; Aisner, D.L.; Akerley, W.; Bauman, J.; Chirieac, L.R.; D’Amico, T.A.; DeCamp, M.M.; Dilling, T.J.; Dobelbower, M.; Doebele, R.C.; Govindan, R.; Gubens, M.A.; Hennon, M.; Horn, L.; Komaki, R.; Lackner, R.P.; Lanuti, M.; Leal, T.A.; Leisch, L.J.; Lilenbaum, R.; Lin, J.; Loo, B.W., Jr; Martins, R.; Otterson, G.A.; Reckamp, K.; Riely, G.J.; Schild, S.E.; Shapiro, T.A.; Stevenson, J.; Swanson, S.J.; Tauer, K.; Yang, S.C.; Gregory, K.; Hughes, M. Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw., 2017, 15(4), 504-535. doi: 10.6004/jnccn.2017.0050 PMID: 28404761
  4. Hirsch, F.R.; Scagliotti, G.V.; Mulshine, J.L.; Kwon, R.; Curran, W.J., Jr; Wu, Y.L.; Paz-Ares, L. Lung cancer: Current therapies and new targeted treatments. Lancet, 2017, 389(10066), 299-311. doi: 10.1016/S0140-6736(16)30958-8 PMID: 27574741
  5. Wang, M.; Herbst, R.S.; Boshoff, C. Toward personalized treatment approaches for non-small-cell lung cancer. Nat. Med., 2021, 27(8), 1345-1356. doi: 10.1038/s41591-021-01450-2 PMID: 34385702
  6. Herbst, R.S.; Morgensztern, D.; Boshoff, C. The biology and management of non-small cell lung cancer. Nature, 2018, 553(7689), 446-454. doi: 10.1038/nature25183 PMID: 29364287
  7. Murugesan, S.; Murugesan, J.; Palaniappan, S.; Palaniappan, S.; Murugan, T.; Siddiqui, S.S.; Loganathan, S. Tyrosine kinase inhibitors (TKIs) in lung cancer treatment: A comprehensive analysis. Curr. Cancer Drug Targets, 2021, 21(1), 55-69. doi: 10.2174/1568009620666201009130008 PMID: 33038912
  8. Chaft, J.E.; Rimner, A.; Weder, W.; Azzoli, C.G.; Kris, M.G.; Cascone, T. Evolution of systemic therapy for stages I-III non-metastatic non-small-cell lung cancer. Nat. Rev. Clin. Oncol., 2021, 18(9), 547-557. doi: 10.1038/s41571-021-00501-4 PMID: 33911215
  9. Boumahdi, S.; de Sauvage, F.J. The great escape: Tumour cell plasticity in resistance to targeted therapy. Nat. Rev. Drug Discov., 2020, 19(1), 39-56. doi: 10.1038/s41573-019-0044-1 PMID: 31601994
  10. Sharifi-Rad, J.; Quispe, C.; Patra, J.K.; Singh, Y.D.; Panda, M.K.; Das, G.; Adetunji, C.O.; Michael, O.S.; Sytar, O.; Polito, L.; Živković, J.; Cruz-Martins, N.; Klimek-Szczykutowicz, M.; Ekiert, H.; Choudhary, M.I.; Ayatollahi, S.A.; Tynybekov, B.; Kobarfard, F.; Muntean, A.C.; Grozea, I.; Daştan, S.D.; Butnariu, M.; Szopa, A.; Calina, D. Paclitaxel: Application in modern oncology and nanomedicine-based cancer therapy. Oxid. Med. Cell. Longev., 2021, 2021, 3687700. doi: 10.1155/2021/3687700 PMID: 34707776
  11. Yoneshima, Y.; Morita, S.; Ando, M.; Nakamura, A.; Iwasawa, S.; Yoshioka, H.; Goto, Y.; Takeshita, M.; Harada, T.; Hirano, K.; Oguri, T.; Kondo, M.; Miura, S.; Hosomi, Y.; Kato, T.; Kubo, T.; Kishimoto, J.; Yamamoto, N.; Nakanishi, Y.; Okamoto, I. Phase 3 trial comparing nanoparticle albumin-bound paclitaxel with docetaxel for previously treated advanced NSCLC. J. Thorac. Oncol., 2021, 16(9), 1523-1532. doi: 10.1016/j.jtho.2021.03.027 PMID: 33915251
  12. Booth, B.W.; Inskeep, B.D.; Shah, H.; Park, J.P.; Hay, E.J.; Burg, K.J.L. Tannic Acid preferentially targets estrogen receptor-positive breast cancer. Int. J. Breast Cancer, 2013, 2013, 369609. doi: 10.1155/2013/369609 PMID: 24369505
  13. Darvin, P.; Joung, Y.H.; Kang, D.Y.; Sp, N.; Byun, H.J.; Hwang, T.S.; Sasidharakurup, H.; Lee, C.H.; Cho, K.H.; Park, K.D.; Lee, H.K.; Yang, Y.M. Tannic acid inhibits EGFR/STAT1/3 and enhances p38/STAT1 signalling axis in breast cancer cells. J. Cell. Mol. Med., 2017, 21(4), 720-734. doi: 10.1111/jcmm.13015 PMID: 27862996
  14. David, J.M.; Owens, T.A.; Barwe, S.P.; Rajasekaran, A.K. Gramicidin A induces metabolic dysfunction and energy depletion leading to cell death in renal cell carcinoma cells. Mol. Cancer Ther., 2013, 12(11), 2296-2307. doi: 10.1158/1535-7163.MCT-13-0445 PMID: 24006494
  15. Chen, T.; Wang, Y.; Yang, Y.; Yu, K.; Cao, X.; Su, F.; Xu, H.; Peng, Y.; Hu, Y.; Qian, F.; Wang, Z. Gramicidin inhibits human gastric cancer cell proliferation, cell cycle and induced apoptosis. Biol. Res., 2019, 52(1), 57. doi: 10.1186/s40659-019-0264-1 PMID: 31767027
  16. Gong, X.; Zou, L.; Wang, M.; Zhang, Y.; Peng, S.; Zhong, M.; Zhou, J.; Li, X.; Ma, X. Gramicidin inhibits cholangiocarcinoma cell growth by suppressing EGR4. Artif. Cells Nanomed. Biotechnol., 2020, 48(1), 53-59. doi: 10.1080/21691401.2019.1699808 PMID: 31852273
  17. David, J.M.; Owens, T.A.; Inge, L.J.; Bremner, R.M.; Rajasekaran, A.K. Gramicidin A blocks tumor growth and angiogenesis through inhibition of hypoxia-inducible factor in renal cell carcinoma. Mol. Cancer Ther., 2014, 13(4), 788-799. doi: 10.1158/1535-7163.MCT-13-0891 PMID: 24493697
  18. Wen, T.; Song, L.; Hua, S. Perspectives and controversies regarding the use of natural products for the treatment of lung cancer. Cancer Med., 2021, 10(7), 2396-2422. doi: 10.1002/cam4.3660 PMID: 33650320
  19. Roskoski, R., Jr Properties of FDA-approved small molecule protein kinase inhibitors: A 2021 update. Pharmacol. Res., 2021, 165, 105463. doi: 10.1016/j.phrs.2021.105463 PMID: 33513356
  20. Elancheran, R.; Saravanan, K.; Divakar, S.; Kumari, S.; Maruthanila, V.L.; Kabilan, S.; Ramanathan, M.; Devi, R.; Kotoky, J. Design, synthesis and biological evaluation of novel 1, 3- thiazolidine-2, 4-diones as anti-prostate cancer agents. Anticancer. Agents Med. Chem., 2017, 17(13), 1756-1768. PMID: 28403781
  21. Hansson, T.; Oostenbrink, C.; van Gunsteren, W. Molecular dynamics simulations. Curr. Opin. Struct. Biol., 2002, 12(2), 190-196. doi: 10.1016/S0959-440X(02)00308-1 PMID: 11959496
  22. Vanommeslaeghe, K.; Hatcher, E.; Acharya, C.; Kundu, S.; Zhong, S.; Shim, J.; Darian, E.; Guvench, O.; Lopes, P.; Vorobyov, I.; Mackerell, A.D. Jr CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J. Comput. Chem., 2010, 31(4), 671-690. PMID: 19575467
  23. Attwood, M.M.; Fabbro, D.; Sokolov, A.V.; Knapp, S.; Schiöth, H.B. Trends in kinase drug discovery: Targets, indications and inhibitor design. Nat. Rev. Drug Discov., 2021, 20(11), 839-861. doi: 10.1038/s41573-021-00252-y PMID: 34354255
  24. Remon, J.; Pignataro, D.; Novello, S.; Passiglia, F. Current treatment and future challenges in ROS1- and ALK-rearranged advanced non-small cell lung cancer. Cancer Treat. Rev., 2021, 95, 102178. doi: 10.1016/j.ctrv.2021.102178 PMID: 33743408
  25. Golding, B.; Luu, A.; Jones, R.; Viloria-Petit, A.M. The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC). Mol. Cancer, 2018, 17(1), 52. doi: 10.1186/s12943-018-0810-4 PMID: 29455675
  26. Hoj, J.P.; Mayro, B.; Pendergast, A.M. TAZ-AXL-ABL2 feed-forward signaling axis promotes lung adenocarcinoma brain metastasis. Cell Rep., 2019, 29(11), 3421-3434.e8. doi: 10.1016/j.celrep.2019.11.018 PMID: 31825826
  27. Gu, J.J.; Hoj, J.; Rouse, C.; Pendergast, A.M. Mesenchymal stem cells promote metastasis through activation of an ABL-MMP9 signaling axis in lung cancer cells. PLoS One, 2020, 15(10), e0241423. doi: 10.1371/journal.pone.0241423 PMID: 33119681
  28. Luttman, J.H.; Hoj, J.P.; Lin, K.H.; Lin, J.; Gu, J.J.; Rouse, C.; Nichols, A.G.; MacIver, N.J.; Wood, K.C.; Pendergast, A.M. ABL allosteric inhibitors synergize with statins to enhance apoptosis of metastatic lung cancer cells. Cell Rep., 2021, 37(4), 109880. doi: 10.1016/j.celrep.2021.109880 PMID: 34706244
  29. Petridou, E.T.; Sergentanis, T.N.; Antonopoulos, C.N.; Dessypris, N.; Matsoukis, I.L.; Aronis, K.; Efremidis, A.; Syrigos, C.; Mantzoros, C.S. Insulin resistance: An independent risk factor for lung cancer? Metabolism, 2011, 60(8), 1100-1106. doi: 10.1016/j.metabol.2010.12.002 PMID: 21251684
  30. Althubiti, M.; Almaimani, R.; Eid, S.Y.; Elzubaier, M.; Refaat, B.; Idris, S.; Alqurashi, T.A.; El-Readi, M.Z. BTK targeting suppresses inflammatory genes and ameliorates insulin resistance. Eur. Cytokine Netw., 2020, 31(4), 168-179. doi: 10.1684/ecn.2020.0454 PMID: 33648925

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Bentham Science Publishers, 2025