Exploring the anticancer activity and active mechanism of turkish propolis against hl-60 myeloid cancer cells: insights from molecular docking studies
Abstract
Turkish propolis has gained significant attention in the medical field due to its diverse biological activities, which are influenced by geographical origin and plant sources. This study aimed to explore the anticancer activity and active mechanism of Turkish propolis collected from the Trabzon region against HL-60 myeloid cancer cells. Computational calculations using the Schrödinger 2021-4 small molecule drug discovery suite were performed, and the three-dimensional structure of caspase-3 (PDB ID: 2C1E) and procaspase-3 (PDB ID: 4JQY) were obtained from the Protein Data Bank. Molecular docking simulations were conducted to investigate the binding pose of the propolis' active ingredients within the caspase-3 binding site and also allosteric site of procaspase-3. The identified binding sites were utilized, and the natural compounds present in the propolis extract, including quercetin, caffeic acid, campherol, galangin, naringenin, and chrysin, were prepared using the LigPrep module. The docking results revealed significant interactions of the active ingredients with amino acid residues in the caspase-3 binding site, highlighting the potential role of ARG207, GLN161, GLY122, and HIE122 in modulating caspase-3 activity. Additionally, in the site-3 binding region, quercetin, kaempferol, and galangin exhibited specific interactions with CYS170 and LYS260. Furtheremore all polyphenolic compouds make several interactions with crucial amino acid residues, especially ARG164 and TYR197 in allosteric site of procaspase-3. These findings provide valuable insights into the active mechanism of Turkish propolis against HL-60 myeloid cancer cells through its interactions with caspase-3 and procaspase-3. Further experimental validation is required to confirm the functional significance of these interactions and their potential as effective anticancer agents. This study contributes to the understanding of Turkish propolis' anticancer potential and supports its potential use as a therapeutic agent against HL-60 myeloid cancer cells.
References
- [1] Society AC. About Acute Myeloid Leukemia (AML). https://www.cancer.org/content/dam/CRC/PDF/Public/8674.00.pdf (accessed on 1 July 2023)
- [2] Stojanović ST, Najman SJ, Popov BB, Najman SJ. Propolis: chemical composition, biological and pharmacological activity–a review. ACTA MEDICA MEDIANAE. 2020; 59(2). doi:10.5633/amm.2020.0215
- [3] Castaldo S, Capasso F. Propolis, an old remedy used in modern medicine. Fitoterapia. 2002; 73(1): 1-6. doi:10.1016/s0367-326x(02)00185-5
- [4] Sforcin JM. Propolis and the immune system: a review. J Ethnopharmacol. 2007; 113(1): 1-14. doi:10.1016/j.jep.2007.05.012
- [5] Premratanachai P, Chanchao C. Review of the anticancer activities of bee products. Asian Pac J Trop Biomed. 2014; 4(5): 337-344. doi:10.12980/APJTB.4.2014C1262
- [6] Elumalai P, Muninathan N, Megalatha ST, Suresh A, Kumar KS, Jhansi N, ... Krishnamoorthy G. An Insight into Anticancer Effect of Propolis and Its Constituents: A Review of Molecular Mechanisms. Evidence-Based Complementary and Alternative Medicine. 2022; 2022: 1-14. https://doi.org/10.1155/2022/5901191
- [7] Bozkuş TN, Değer O, Yaşar A. Chemical characterization of water and ethanolic extracts of Turkish propolis by HPLC-DAD and GCMS. Journal of Liquid Chromatography & Related Technologies. 2021; 44: 77-86. doi:10.1080/10826076.2021.1883648
- [8] O'Donovan N, Crown J, Stunell H, Hill ADK, McDermott E, O'Higgins N, Duffy MJ. Caspase 3 in breast cancer. Clinical Cancer Research. 2023; 9(2): 738-742. Retrieved from <Go to ISI>://WOS:000180840200029
- [9] Shen A, Lupardus PJ, Albrow VE, Guzzetta A, Powers JC, Garcia KC, Bogyo M. Mechanistic and structural insights into the proteolytic activation of Vibrio cholerae MARTX toxin. Nature Chemical Biology. 2009; 5: 469-478. doi:10.1038/nchembio.178
- [10] Staff D. Selecting prescalers for PLL synthesizers. Microwaves & RF. 2001; 40(9): 102. Retrieved from <Go to ISI>://WOS:000171293600020
- [11] Halgren TA. Identifying and Characterizing Binding Sites and Assessing Druggability. Journal of Chemical Information and Modeling. 2009; 49(2): 377-389. doi:10.1021/ci800324m
- [12] Ucar M, Deger O, Gerigelmez AY, Cengiz S, Barlak Y, Ovali E. Effect of Turkish pollen and propolis extracts on caspase-3 activity in myeloid cancer cell lines. Tropical Journal of Pharmaceutical Research. 2016; 15(11): 2445-2449. doi:10.4314/tjpr.v15i11.20
- [13] Nwaefulu ON, Al-Shar'i NA, Owolabi JO, Sagineedu SR, Woei LC, Wai LK, ... Stanslas J. The impact of cycleanine in cancer research: a computational study. Journal of Molecular Modeling. 2022; 28(11). doi:10.1007/s00894-022-05326-1
- [14] Mohanty M, Mohanty PS. Molecular docking in organic, inorganic, and hybrid systems: a tutorial review. Monatshefte für Chemie. 2023; 154(7): 683-707. doi:10.1007/s00706-023-03076-1
- [15] Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews. 1997; 23(1-3): 3-25.
- [16] Leite NB, Martins DB, Alvares DS, dos Santos Cabrera MP. Quercetin induces lipid domain-dependent permeability. Chemistry and Physics of Lipids. 2022; 242. doi:10.1016/j.chemphyslip.2021.105160
- [17] Başoğlu-Ünal F, Tufan S, Tan N. Natural phenolic compounds from Satureja L. as inhibitors of COVID-19 protease (Mpro): Computational investigations. International Journal of Plant Based Pharmaceuticals. 2022; 2(1): 111-117.
Details
| Primary Language | English |
|---|---|
| Subjects | Pharmacology and Pharmaceutical Sciences (Other) |
| Journal Section | Articles |
| Authors | |
| Publication Date | June 28, 2025 |
| Published in Issue | Year 2023 Volume: 27 Issue: 5 |