In silico Computational Study of Cinnamon (Cinnamomum verum) Bioactive Compounds as Cancer-Immunotherapy Drug Candidate Targeting RAS-JAK-ERK Signaling Pathway to Inhibit the Programmed Death Protein Ligand 1 (PD-L1) Expression
DOI:
https://doi.org/10.29356/jmcs.v69i4.2241Keywords:
Cancer-immunotherapy, ERK, JAK, PD-L1, RASAbstract
Abstract. Immunotherapy is the current and an alternative therapy option for cancer. Targeting PD-L1 expression provides one approach for limiting cancer progression. Cinnamon is a plant with medicinal properties that is also commonly used as a spice. Previous study indicates that cinnamon has multiple therapeutic effects because it is utilized to treat a variety of diseases. The purpose of this research is to examine the potential of bioactive compounds derived from cinnamon as potential cancer immunotherapy agents through the inhibition of PD-L1 expression. In the present investigation, in silico approaches were used, which included molecular docking and predicting the biological activity of cinnamon bioactive compounds. According to the findings, the active compound of cinnamon was effective and had the potential to inhibit the JAK protein, but not RAS or ERK. Furthermore, according to the biological activity predictions, cinnamon bioactive compounds contribute as cancer fighting agents by having high Pa values for several parameters such as antineoplastic, apoptosis agonist, BRAF expression inhibitor, JAK2 expression inhibitor, and Myc inhibitor also low Pa values for M-CSF agonists. Finally, more detailed research on cinnamon bioactive compounds, particularly caryophyllene, is required.
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1. Siegel, R. L.; Miller, K. D.; Wagle, N. S.; Jemal, A. CA Cancer J. Clin. 2023, 73, 17–48.
2. Rahib, L.; Wehner, M. R.; Matrisian, L. M.; Nead, K. T. JAMA Netw. Open. 2021, 4, e214708.
3. Lewandowska, A. M.; Rudzki, M.; Rudzki, S.; Lewandowski, T.; Laskowska, B. Ann. Agric. Environ. Med. 2019, 26, 1–7.
4. Akinyemiju, T.; Wiener, H.; Pisu, M. BMC Cancer. 2017, 17, 597.
5. Debela, D. T.; Muzazu, S. G.; Heraro, K. D.; Ndalama, M. T.; Mesele, B. W.; Haile, D. C.; Kitui, S. K.; Manyazewal, T. SAGE Open Med. 2021, 9, 20503121211034308.
6. Stub, T.; Quandt, S. A.; Arcury, T. A.; Sandberg, J. C.; Kristoffersen, A. E. BMC Health Serv. Res. 2018, 18, 854.
7. Makuku, R.; Khalili, N.; Razi, S.; Keshavarz-Fathi, M.; Rezaei, N. J. Immunol. Res. 2021, 2021, 6661406.
8. Shiravand, Y.; Khodadadi, F.; Kashani, S. M. A.; Hosseini-Fard, S. R.; Hosseini, S.; Sadeghirad, H.; Ladwa, R.; O’Byrne, K.; Kulasinghe, A. Curr. Oncol. 2022, 29, 3044–3060.
9. Zhao, T.; Li, Y.; Zhang, J.; Zhang, B. Oncol. Lett. 2020, 20, 1127–1134.
10. Gao, Z.; Chen, J. F.; Li, X. G.; Shi, Y. H.; Tang, Z.; Liu, W. R.; Zhang, X.; Huang, A.; Luo, X. M.; Gao, Q.; Shi, G. M.; Ke, A. W.; Zhou, J.; Fan, J.; Fu, X. T.; Ding, Z. B. Cancer Cell Int. 2022, 22, 1–12.
11. Su, C.; Wang, H.; Liu, Y.; Guo, Q.; Zhang, L.; Li, J.; Zhou, W.; Yan, Y.; Zhou, X.; Zhang, J. Front. Oncol. 2020, 10, 554313.
12. Martins, F.; Sofiya, L.; Sykiotis, G. P.; Lamine, F.; Maillard, M.; Fraga, M.; Shabafrouz, K.; Ribi, C.; Cairoli, A.; Guex-Crosier, Y.; Kuntzer, T.; Michielin, O.; Peters, S.; Coukos, G.; Spertini, F.; Thompson, J. A.; Obeid, M. Nat. Rev. Clin. Oncol. 2019, 16, 563–580.
13. Putra, W. E.; Mentari, A. M. L. S.; Ratnasari, D.; Chairunniza, D.; Hidayatullah, A.; Rifa’i, M. FABAD J. Pharm. Sci. 2024, 49, 91–110.
14. Li, T. F.; Hwang, I. H.; Tsai, C. H.; Hwang, S. J.; Wu, T. P.; Chen, F. P. J. Chin. Med. Assoc. 2023, 86, 767–774.
15. Putra, W. E.; Agusinta, A. K.; Ashar, M. S. A. A.; Manullang, V. A.; Rifa’i, M. K. Int. J. Mod. Sci. 2023, 9, 1–14.
16. Amrati, F. E.; Bourhia, M.; Slighoua, M.; Mohammad, S. A.; Alzahrani, A.; Ullah, R.; Bari, A.; Bousta, D. Saudi Pharm. J. 2021, 29, 1185–1204.
17. Putra, W. E.; Maulana, A. R.; Ramadhan, A. T. K.; Rifa’i, M. J. Herbmed Pharmacol. 2020, 9, 408–411.
18. Putra, W. E.; Rifa’i, M. Adv. Pharm. Bull. 2019, 9, 619–623.
19. Xiang, Y.; Guo, Z.; Zhu, P.; Chen, J.; Huang, Y. Cancer Med. 2019, 8, 1958–1975.
20. Yin, S. Y.; Wei, W. C.; Jian, F. Y.; Yang, N. S. Evid. Based Complement. Alternat. Med. 2013, 2013, 302426.
21. Rao, P. V.; Gan, S. H. Evid. Based Complement. Alternat. Med. 2014, 2014, 642942.
22. Gruenwald, J.; Freder, J.; Armbruester, N. Crit. Rev. Food Sci. Nutr. 2010, 50, 822–834.
23. Kwon, H. K.; Jeon, W. K.; Hwang, J. S.; Lee, C. G.; So, J. S.; Park, J. A.; Ko, B. S.; Im, S. H. Cancer Lett. 2009, 278, 174–182.
24. Arora, S.; Gusain, M. P.; Gunupuru, R.; Kaushik, R.; Sinha, P.; Kumar, D. Eur. J. Mol. Clin. Med. 2021, 8, 1–15.
25. Hidayatullah, A.; Putra, W. E.; Sustiprijatno; Widiastuti, D.; Salma, W. O.; Heikal, M. F. Trends Sci. 2023, 20, 1–12.
26. Putra, W. E. FTSTJ. 2018, 3, 682–685.
27. Putra, W. E.; Agustin, F.; Rochmatika, L.; Salma, W. O. Malays. J. Biochem. Mol. Biol. 2019, 1, 152–154.
28. Hidayatullah, A.; Putra, W. E.; Sustiprijatno; Permatasari, G. W.; Salma, W. O.; Widiastuti, D.; Susanto, H.; Muchtaromah, B.; Sari, D. R. T.; Ningsih, F. N.; Heikal, M. F.; Yusuf, A. M. R.; Arizona, A. S. Chiang Mai Univ. J. Nat. Sci. 2021, 20, 1–20.
29. Putra, W. E.; Salma, W. O.; Rifa’i, M. Nat. Prod. Sci. 2019, 25, 215–221.
30. Hidayatullah, A.; Putra, W. E.; Salma, W. O.; Muchtaromah, B.; Permatasari, G. W.; Susanto, H.; Widiastuti, D.; Kismurtono, M. Chiang Mai Univ. J. Nat. Sci. 2021, 20, 1–17.
31. Putra, W. E.; Waffareta, E.; Ardiana, O.; Januarisasi, I. D.; Soewondo, A.; Rifa’i, M. Biosci. Res. 2017, 14, 201–213.
32. Yi, M.; Niu, M.; Xu, L.; Luo, S.; Wu, K. J. Hematol. Oncol. 2021, 14, 10.
33. Dong, Y.; Sun, Q.; Zhang, X. Oncotarget. 2017, 8, 2171–2186.
34. Zerdes, I.; Matikas, A.; Bergh, J.; Rassidakis, G. Z.; Foukakis, T. Oncogene. 2018, 37, 4639–4661.
35. Bardhan, K.; Anagnostou, T.; Boussiotis, V. A. Front. Immunol. 2016, 7, 550.
36. McDonald, J.; Lambert, D. G. BJA Educ. 2022, 22, 20–25.
37. Dror, R. O.; Pan, A. C.; Arlow, D. H.; Borhani, D. W.; Maragakis, P.; Shan, Y.; Xu, H.; Shaw, D. E. Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 13118–13123.
38. Terefe, E. M.; Ghosh, A. Bioinform. Biol. Insights. 2022, 16, 11779322221125605.
39. Owoloye, A. J.; Ligali, F. C.; Enejoh, O. A.; Musa, A. Z.; Aina, O.; Idowu, E. T.; Oyebola, K. M. PLoS One. 2022, 17, e0268269.
40. Pichler, W. J.; Adam, J.; Watkins, S.; Wuillemin, N.; Yun, J.; Yerly, D. Int. Arch. Allergy Immunol. 2015, 168, 13–24.
41. Cascorbi, I. Dtsch. Arztebl. Int. 2012, 109, 546–555.
42. van Roon, E. N.; Flikweert, S.; le Comte, M.; Langendijk, P. N.; Kwee-Zuiderwijk, W. J.; Smits, P.; Brouwers, J. R. Drug Saf. 2005, 28, 1131–1139.
43. Alekseeva, I. V.; Kuznetsova, A. A.; Bakman, A. S.; Fedorova, O. S.; Kuznetsov, N. A. Biochim. Biophys. Acta Gen. Subj. 2020, 1864, 129718.
44. Kulandaisamy, A.; Lathi, V.; ViswaPoorani, K.; Yugandhar, K.; Gromiha, M. M. Int. J. Biol. Macromol. 2017, 94, 438–444.
45. Luo, Z.; Liu, C.; Quan, P.; Yang, D.; Zhao, H.; Wan, X.; Fang, L. Acta Pharm. Sin. B. 2020, 10, 928–945.
46. Hutchins, K. M. R. Soc. Open Sci. 2018, 5, 180564.
47. Chen, D.; Oezguen, N.; Urvil, P.; Ferguson, C.; Dann, S. M.; Savidge, T. C. Sci. Adv. 2016, 2, e1501240.
48. Patil, R.; Das, S.; Stanley, A.; Yadav, L.; Sudhakar, A.; Varma, A. K. PLoS One. 2010, 5, e12029.
49. Sarkar, A.; Kellogg, G. E. Curr. Top. Med. Chem. 2010, 10, 67–83.
50. Hanahan, D. Cancer Discov. 2022, 12, 31–46.
51. Ravi, S.; Alencar, A. M., Jr.; Arakelyan, J.; Xu, W.; Stauber, R.; Wang, C. I.; Papyan, R.; Ghazaryan, N.; Pereira, R. M. Cureus. 2022, 14, e24803.
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Copyright (c) 2025 Wira Eka Putra, Sustiprijatno , Arief Hidayatullah, Diana Widiastuti, Muhammad Fikri Heikal
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