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Plant Science Today (PST)

Research Articles

Vol. 12 No. 4 (2025)

Investigating the therapeutic potential of Tabernaemontana alternifolia bark for managing lung squamous cell carcinoma

DOI
https://doi.org/10.14719/pst.9962
Submitted
10 June 2025
Published
25-09-2025 — Updated on 16-10-2025
Versions

Abstract

The high global incidence and mortality rates of Lung Squamous Cell Carcinoma (LUSC) are extremely concerning. Current therapeutic strategies face significant challenges, including drug toxicity and the growing resistance to Food and Drug Administration approved medications, underscoring the urgent need for novel treatment options. Notably, natural alkaloids extracted from the plant Tabernaemontana alternifolia have exhibited promising anticancer effects across various cancer types. In this work, we focused on the molecular targets of LUSC for phytochemicals from T. alternifolia bark (TAB) and evaluated their potential as a therapeutic line for its treatment. A network pharmacology analysis was conducted to identify the molecular targets and pathways relevant to LUSC therapy. Additionally, validation of these findings through docking studies have been done. Results revealed that in-silico docking tests using AutoDock Vina, the plant's compounds 9-methoxycamptothecin, camptothecin and heyneanine demonstrated the ability to inhibit LUSC cell proliferation and induce apoptosis. These compounds suppressed genes involved in crucial cellular processes such as proliferation, angiogenesis, DNA repair and cell cycle control, which contribute to cancer management. Additionally, they also have the potential to inhibit the expression of key oncogenic factors, including MET, KDR and MMPs. This work provides significant insights into the molecular mechanisms underlying the anticancer effects of these compounds in LUSC. It suggests that they could be a promising novel therapeutic approach for combating LUSC soon. However, the safety and efficacy of TAB phytochemicals for LUSC treatment must be thoroughly validated through adequate preclinical and clinical trials.

References

  1. 1. Chaitanya Thandra K, Barsouk A, Saginala K, Sukumar Aluru J, Barsouk A. Epidemiology of lung cancer. Współczesna Onkol. 2021;25(1):45-52.
  2. 2. Relli V, Trerotola M, Guerra E, Alberti S. Abandoning the notion of non-small cell lung cancer. Trends Mol Med. 2019;25(7):585-94. https://doi.org/10.1016/j.molmed.2019.04.012
  3. 3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. https://doi.org/10.3322/caac.21551
  4. 4. Naidoo CM, Naidoo Y, Dewir YH, Murthy HN, El-Hendawy S, Al-Suhaibani N. Major bioactive alkaloids and biological activities of Tabernaemontana species (Apocynaceae). Plants. 2021;10(2):313. https://doi.org/10.3390/plants10020313
  5. 5. Silveira D, de Melo AMMF, Magalhães PO, Fonseca-Bazzo YM. Tabernaemontana species: promising sources of new useful drugs. In: 2017:227-89. https://doi.org/10.1016/B978-0-444-63929-5.00007-3
  6. 6. Dey A, Mukherjee A, Chaudhury M. Alkaloids from Apocynaceae. In: 2017:373-488. https://doi.org/10.1016/B978-0-444-63931-8.00010-2
  7. 7. Chandran U, Mehendale N, Patil S, Chaguturu R, Patwardhan B. Network pharmacology. In: Innovative approaches in drug discovery. Elsevier; 2017:127-64. https://doi.org/10.1016/B978-0-12-801814-9.00005-2
  8. 8. Mohanraj K, Karthikeyan BS, Vivek-Ananth RP, Chand RPB, Aparna SR, Mangalapandi P, et al. IMPPAT: a curated database of Indian medicinal plants, phytochemistry and therapeutics. Sci Rep. 2018;8(1):4329. https://doi.org/10.1038/s41598-018-22631-z
  9. 9. 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.2c07611
  10. 10. Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2023 update. Nucleic Acids Res. 2023;51(D1):D1373-80. https://doi.org/10.1093/nar/gkac956
  11. 11. Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 2019;47(W1):W357-64. https://doi.org/10.1093/nar/gkz382
  12. 12. 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
  13. 13. Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607-13. https://doi.org/10.1093/nar/gky1131
  14. 14. Lopes CT, Franz M, Kazi F, Donaldson SL, Morris Q, Bader GD. Cytoscape Web: an interactive web-based network browser. Bioinformatics. 2010;26(18):2347-8. https://doi.org/10.1093/bioinformatics/btq430
  15. 15. Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014;8(S4):S11. https://doi.org/10.1186/1752-0509-8-S4-S11
  16. 16. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498-504. https://doi.org/10.1101/gr.1239303
  17. 17. Berman HM. The protein data bank. Nucleic Acids Res. 2000;28(1):235-42. https://doi.org/10.1093/nar/28.1.235
  18. 18. O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: an open chemical toolbox. J Cheminform. 2011;3(1):33. https://doi.org/10.1186/1758-2946-3-33
  19. 19. 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
  20. 20. Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0: new docking methods, expanded force field and Python bindings. J Chem Inf Model. 2021;61(8):3891-8. https://doi.org/10.1021/acs.jcim.1c00203
  21. 21. Ge SX, Jung D, Yao R. ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics. 2020;36(8):2628-9. https://doi.org/10.1093/bioinformatics/btz931
  22. 22. Nawaz M, Shah N, Zanetti B, Maugeri M, Silvestre R, Fatima F, et al. Extracellular vesicles and matrix remodeling enzymes: the emerging roles in extracellular matrix remodeling, progression of diseases and tissue repair. Cells. 2018;7(10):167. https://doi.org/10.3390/cells7100167
  23. 23. Acha-Sagredo A, Uko B, Pantazi P, Bediaga NG, Moschandrea C, Rainbow L, et al. Long non-coding RNA dysregulation is a frequent event in non-small cell lung carcinoma pathogenesis. Br J Cancer. 2020;122(7):1050-8. https://doi.org/10.1038/s41416-020-0740-9
  24. 24. Liu Y, Yuan M, Xu B, Gao R, You Y, Wang Z, et al. ANKRD49 promotes the invasion and metastasis of lung adenocarcinoma via a P38/ATF-2 signalling pathway. J Cell Mol Med. 2022;26(16):4401-15. https://doi.org/10.1111/jcmm.17551
  25. 25. Alam M, Hasan GM, Eldin SM, Adnan M, Riaz MB, Islam A, et al. Investigating regulated signaling pathways in therapeutic targeting of non-small cell lung carcinoma. Biomed Pharmacother. 2023;161:114452. https://doi.org/10.1016/j.biopha.2023.114452
  26. 26. Huang B, Lang X, Li X. The role of IL-6/JAK2/STAT3 signaling pathway in cancers. Front Oncol. 2022;12:1092908. https://doi.org/10.3389/fonc.2022.1092908
  27. 27. Navale GR, Singh S, Ghosh K. NO donors as the wonder molecules with therapeutic potential: recent trends and future perspectives. Coord Chem Rev. 2023;481:215052. https://doi.org/10.1016/j.ccr.2022.215052
  28. 28. Li G, Jin X, Zheng J, Jiang N, Shi W. UCH-L3 promotes non-small cell lung cancer proliferation via accelerating cell cycle and inhibiting cell apoptosis. Biotechnol Appl Biochem. 2021;68(1):165-72. https://doi.org/10.1002/bab.1924
  29. 29. Gómez-López S, Whiteman ZE, Janes SM. Mapping lung squamous cell carcinoma pathogenesis through in vitro and in vivo models. Commun Biol. 2021;4(1):937. https://doi.org/10.1038/s42003-021-02534-0
  30. 30. Anusewicz D, Orzechowska M, Bednarek AK. Lung squamous cell carcinoma and lung adenocarcinoma differential gene expression regulation through pathways of Notch, Hedgehog, Wnt and ErbB signalling. Sci Rep. 2020;10(1):21128. https://doi.org/10.1038/s41598-020-78222-8
  31. 31. Wang Y, Luo W, Wang Y. PARP-1 and its associated nucleases in DNA damage response. DNA Repair (Amst). 2019;81:102651. https://doi.org/10.1016/j.dnarep.2019.102651
  32. 32. Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nat Rev Mol Cell Biol. 2002;3(9):639-50. https://doi.org/10.1038/nrm908
  33. 33. Bar-Shavit R, Maoz M, Kancharla A, Nag J, Agranovich D, Grisaru-Granovsky S, et al. G protein-coupled receptors in cancer. Int J Mol Sci. 2016;17(8):1320. https://doi.org/10.3390/ijms17081320
  34. 34. Dorsam RT, Gutkind JS. G-protein-coupled receptors and cancer. Nat Rev Cancer. 2007;7(2):79-94. https://doi.org/10.1038/nrc2069
  35. 35. Arafeh R, Samuels Y. PIK3CA in cancer: the past 30 years. Semin Cancer Biol. 2019;59:36-49. https://doi.org/10.1016/j.semcancer.2019.02.002
  36. 36. Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010;141(7):1117-34. https://doi.org/10.1016/j.cell.2010.06.011
  37. 37. Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, et al. Oncogenic signaling pathways in The Cancer Genome Atlas. Cell. 2018;173(2):321-37. https://doi.org/10.1016/j.cell.2018.03.035
  38. 38. Burris HA. Overcoming acquired resistance to anticancer therapy: focus on the PI3K/AKT/mTOR pathway. Cancer Chemother Pharmacol. 2013;71(4):829-42. https://doi.org/10.1007/s00280-012-2043-3
  39. 39. Niu Z, Jin R, Zhang Y, Li H. Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials. Signal Transduct Target Ther. 2022;7(1):353. https://doi.org/10.1038/s41392-022-01248-w
  40. 40. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003;3(1):11-22. https://doi.org/10.1038/nrc969
  41. 41. Zoi V, Kyritsis AP, Galani V, Lazari D, Sioka C, Voulgaris S, Alexiou GA. The role of curcumin in cancer: a focus on the PI3K/Akt pathway. Cancers (Basel). 2024;16(8):1554. https://doi.org/10.3390/cancers16081554
  42. 42. Almatroodi SA, Alsahli MA, Rahmani AH. Berberine: an important emphasis on its anticancer effects through modulation of various cell signaling pathways. Molecules. 2022;27(18):5889. https://doi.org/10.3390/molecules27185889

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