Skip to main navigation menu Skip to main content Skip to site footer
Plant Science Today (PST)

Research Articles

Vol. 12 No. Sp2 (2025): Current Trends in Plant Science and Microbiome for Sustainability

Unravelling the potential of Diospyros species in the treatment of pancreatic adenocarcinoma using an in-silico approach

DOI
https://doi.org/10.14719/pst.6346
Submitted
26 November 2024
Published
06-04-2025

Abstract

Pancreatic cancer remains one of the fatal malignancies with limited treatment options and a high rate of drug resistance. Y-box binding protein 1 (YBX1) plays an essential role in pancreatic cancer by upregulating the low- density lipoprotein receptor-related protein-1 (LRP1), which promotes tumour growth through the Wnt/?- catenin pathway. Diospyros genus exhibits anticancer properties and could be used to overcome drug resistance and inhibit pancreatic ductal adenocarcinoma (PDAC). The Cancer Genome Atlas (TCGA) data and TNMplot were analyzed to perform bioinformatics analyses to investigate LRP1 gene alterations and their correlation with YBX1 in PDAC. Diospyros phytochemicals with high binding affinities for YBX1 (PDB ID: 6KTC) were screened through molecular docking. Further, these phytochemicals' pharmacokinetics, drug likeness and toxicity were evaluated using ADMETlab 2.0 and ProTox 3.0. According to bioinformatics analysis, the expression of YBX1 and LRP1 in PDAC samples were significantly correlated. Molecular docking identified 13 phytochemicals with high binding affinities (? -7.5 kcal/mol) for YBX1.Diospyrin (-9.1 kcal/mol), Kaempferol (-7.5 kcal/mol), Mamegakinone (-9.1 kcal/mol) and Neodiospyrin (-8.6 kcal/mol) showed favourable interactions. ADMET analysis confirmed that these four compounds exhibited drug-like properties. Diosprin and Kaempferol have established anticancer effects by inducing apoptosis and inhibiting carcinogenic pathways; however, Mamegakinone and Neodiospyrins’ roles need further investigation using experimental studies. The promising binding affinities of these compounds suggest potential therapeutic applications in PDAC. This study highlights the potential of phytochemicals in the genus Diospyros as potential therapeutic molecules against YBX1 in PDAC.

References

  1. Tiwari PK, Shanmugam P, Karn V, Gupta S, Mishra R, Rustagi S, et al. Extracellular vesicular miRNA in pancreatic cancer: from lab to therapy. Cancers. 2024;16(12):2179–79. https://doi.org/10.3390/cancers16122179
  2. Glaß M, Michl P, Hüttelmaier S. RNA binding proteins as drivers and therapeutic target candidates in pancreatic ductal adenocarcinoma. Int J Mole Sci. 2020;21(11):4190. https://doi.org/10.3390/ijms21114190
  3. Liu Z, Li Y, Li X, Zhao J, Wu S, Wu H, et al. Overexpression of YBX1 Promotes pancreatic ductal adenocarcinoma growth via the GSK3B/Cyclin D1/Cyclin E1 pathway. Mole Thera Onco. 2020;17:21–30. https://doi.org/10.1016/j.omto.2020.03.006
  4. Hayashi A, Hong J, Iacobuzio-Donahue CA. The pancreatic cancer genome revisited. Nature Rev Gastroent Hepatol. 2021;18(7):469–81. https://doi.org/10.1038/s41575-021-00463-z
  5. Vahideh M, Niloufar R, Seyedeh MH, Mahmood B, Abbas R, Mahmoud RJ, et al. Novel EPR-enhanced strategies for targeted drug delivery in pancreatic cancer: An update. J Drug Del Sci Tech. 2022;73:103459. https://doi.org/10.1016/j.jddst.2022.103459
  6. Li Z, Chen H, Li B, Wang T, Ji S, Qin Y, et al. Holistic anti-tumor resistance mechanism of YBX1 and its potential as a chemoresistance target in pancreatic ductal adenocarcinoma. Hol Inte Onco. 2023;2(1):16. https://doi.org/10.1007/s44178-023-00039-8
  7. Kishikawa T, Otsuka M, Yoshikawa T, Ohno M, Ijichi H, Koike K. Satellite RNAs promote pancreatic oncogenic processes via the dysfunction of YBX1. Nature Commun. 2016;7(1):13006. https://doi.org/10.1038/ncomms13006
  8. Campion O, Khalifa TA, Langlois B, Thevenard-Devy J, Stéphanie Salesse, Savary K, et al. Contribution of the low-density lipoprotein receptor family to breast cancer progression. Front Oncol. 2020;10. https://doi.org/10.3389/fonc.2020.00882
  9. Xing P, Liao Z, Ren Z, Zhao J, Song F, Wang G, et al. Roles of low-density lipoprotein receptor-related protein 1 in tumors. Chin J Cancer. 2016;35:1–8. https://doi.org/10.1186/s40880-015-0064-0
  10. Li B, Xing F, Wang J, Wang X, Zhou C, Fan G, et al. YBX1 as a therapeutic target to suppress the LRP1-?-catenin-RRM1 axis and overcome gemcitabine resistance in pancreatic cancer. Cancer Lett. 2024;217197. https://doi.org/10.1016/j.canlet.2024.217197
  11. Singh N, Sharma P, Pal MK, Kahera R, Badoni H, Pant K, et al. In-silico studies targeting the drug-resistant outer membrane proteins of E. Coli with possible monoterpenes from essential oils. 2024 Jan 1 [cited 2024 Sep 12]; https://doi.org/10.2139/ssrn.4683906
  12. Akash S, Bay?l I, Mahmood S, Mukerjee N, Mili TA, Kuldeep D, et al. Mechanistic inhibition of gastric cancer-associated bacteria Helicobacter pylori by selected phytocompounds: A new cutting-edge computational approach. Heliyon. 2023;9(10):e20670. https://doi.org/10.1016/j.heliyon.2023.e20670
  13. Patwa N, Chauhan R, Chauhan A, Kumar M, Ramniwas S, Mathkor DM, et al. Garcinol in gastrointestinal cancer prevention: recent advances and future prospects. J Cancer Res Clin Onco. 2024 Jul 27;150(7):370. https://doi.org/10.1007/s00432-024-05880-6
  14. Butt SM, Sultan TM, Aziz M, Naz A, Ahmed W, Kumar N, et al. Hidden phytochemicals and health claims. Excli J. 2015;14:542–61.
  15. Hanasaki Y, Ogawa S, Fukui S. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Rad Biol Med. 1994;16(6):845–50. https://doi.org/10.1016/0891-5849(94)90202-X
  16. Rauf A, Akram Z, Hafeez N, Khalil AA, Khalid A, Abid Z, et al. Anticancer therapeutic potential of genus Diospyros: From phytochemistry to clinical applications—A review. Food Sci Nutr. 2024;12(10):7033–47. https://doi.org/10.1002/fsn3.4375
  17. Ko H, Huh G, Jung SH, Kwon H, Jeon Y, Park YN, et al. Diospyros kaki leaves inhibit HGF/Met signaling-mediated EMT and stemness features in hepatocellular carcinoma. Food Chemi Toxicol. 2020 Aug 1 [cited 2023 Sep 29];142:111475. https://doi.org/10.1016/j.fct.2020.111475
  18. Alex AT, Nawagamuwa NH, Joseph A, Rao JV, Mathew JA, Udupa N. In vitro anticancer and antioxidant activity of different fractions of Diospyros peregrina unripe fruit extract. Free Radicals and Antioxidants. 2012 Oct;2(4):45–49. https://doi.org/10.5530/ax.2012.4.8
  19. Kawakami S, Nishida S, Nobe A, Inagaki M, Nishimura M, Matsunami K, et al. Eight ent-kaurane diterpenoid glycosides named diosmariosides a–h from the leaves of Diospyros maritima and their cytotoxic activity. Chem Pharmaceu Bull. 2018;66(11):1057–64. https://doi.org/10.1248/cpb.c18-00529
  20. Kim HS, Suh JS, Jang YK, Ahn SH, Raja G, Kim JC, et al. Anticancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway. Sci Rep. 2020;10(1):18119. https://doi.org/10.1038/s41598-020-75140-3
  21. Nuzzo G, Senese G, Gallo C, Albiani F, Romano L, d’Ippolito G, et al. Antitumor potential of immunomodulatory natural products. Marine Drugs. 2022 Jun 8;20(6):386. https://doi.org/10.3390/md20060386
  22. Rauf A, Uddin G, Patel S, Khan A, Halim SA, Bawazeer S, et al. Diospyros, an under-utilized, multi-purpose plant genus: A review. Biomed and Pharmacotherapy. 2017;91:714–30. https://doi.org/10.1016/j.biopha.2017.05.012
  23. Chen TV, Nghia NT, Van L, Linh. Ethnomedicinal, phytochemical and pharmacological properties of Diospyros mollis Griff.: a review. Nat Prod Commun. 2024 Feb 1;19(2):1–21. https://doi.org/10.1177/1934578X241233459
  24. Sujatha V, Kaviyasri G, Venkatesan A, Thirunavukkarasu C, Acharya S, Dayel SB, et al. Biomimetic formation of silver oxide nanoparticles through Diospyros montana bark extract: Its application in dye degradation, antibacterial and anticancer effect in human hepatocellular carcinoma cells. J King Saud Uni. 2023;35(3):102563.
  25. https://doi.org/10.1016/j.jksus.2023.102563
  26. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cbioportal. Sci Signal. 2013;6(269):1–1. https://doi.org/10.1126/scisignal.2004088
  27. Bartha Á, Gy?rffy B. TNMplot.com: a web tool for the comparison of gene expression in normal, tumor and metastatic tissues. Int J Mol Sci. 2021;22(5):2622. https://doi.org/10.3390/ijms22052622
  28. Zou F, Tu R, Duan B, Yang Z, Ping Z, Song X, et al. Drosophila YBX1 homolog YPS promotes ovarian germ line stem cell development by preferentially recognizing 5-methylcytosine RNAs. Proceed Nat Acad Sci. 2020;117(7):3603–9. https://doi.org/10.1073/pnas.1910862117
  29. Vivek-Ananth RP, Mohanraj K, Sahoo AK, Samal A. IMPPAT 2.0: An enhanced and expanded phytochemical Atlas of Indian medicinal plants. ACS Omega. 2023;8(9):8827–45. https://doi.org/10.1021/acsomega.3c00156
  30. Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2025 update. Nucleic Acids Res. 2025;53:D1516–25. https://doi.org/10.1093/nar/gkae1059
  31. Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods in Mole Biol. 2014 Dec 22;1263:243–50. https://doi.org/10.1007/978-1-4939-2269-7_19
  32. BIOVIA. Dassault Systèmes. Discovery Studio Visualizer, v21.1.0.20298[internet]; Dassault Systèmes: San Diego, CA, USA; 2021 Available online: https://discover.3ds.com/discovery-studio-visualizer-download (accessed on 21 December 2021)
  33. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7(1):1–13. https://doi.org/10.1038/srep42717
  34. Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, et al. ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res (Internet). 2021 Apr 24;49(W1):W5–14. https://doi.org/10.1093/nar/gkab255
  35. Banerjee P, Kemmler E, Dunkel M, Preissner R. ProTox 3.0: a webserver for the prediction of toxicity of chemicals. Nuc Acids Res. 2024;52:W513–20. https://doi.org/10.1093/nar/gkae303
  36. Priyadarshini G, Sukumaran G, Dilipan E, Ramani P. Targeting oral cancer: In Silico docking studies of phytochemicals on oncogenic molecular markers. As Pac J Can Preven. 2024;25(6):2069–75. https://doi.org/10.31557/APJCP.2024.25.6.2069
  37. Rauf A, Akram Z, Hafeez N, Khalil AA, Khalid A, Hemeg HA, et al. Anticancer potential of diospyrin and its analogues: an updated review. Food Sci Nutr. 2024;12(9):6047–54. https://doi.org/10.1002/fsn3.4237
  38. Choudhary R, Singh A, Upadhyay A, Singh R, Thangalakshmi S, Dar AH, et al. Exotic god fruit, persimmon (Diospyros kaki): Pharmacological importance and human health aspects. eFood. 2022;4(1):e52. https://doi.org/10.1002/efd2.52

Downloads

Download data is not yet available.