The Potential Mechanism of Ursolic Acid in the Treatment of Bladder Cancer Based on Network Pharmacology and Molecular Docking

Overview

Journal J Int Med Res

Publisher Sage Publications

Specialty General Medicine

Date 2024 Mar 5

PMID 38443785

Authors

Xiao-Long Huang

Yan Sun

Peng Wen

Jun-Cheng Pan

Wei-Yang He

Affiliations

Soon will be listed here.

Abstract

Objective: This study explored the potential molecular mechanisms of ursolic acid (UA) in bladder cancer treatment using network pharmacology and molecular docking.

Methods: The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were used to screen potential targets of UA. Relevant bladder cancer target genes were extracted using the GeneCards database. All data were pooled and intercrossed to obtain common target genes of UA and bladder cancer. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Molecular docking was conducted to verify the possible binding conformation between UA and bladder cancer cells. Then, experiments were performed to further validate the predicted results.

Results: UA exerts anti-tumor effects on bladder cancer through multiple targets and pathways. Molecular docking indicated that UA undergoes stable binding with the proteins encoded by the top six core genes ( and ). The experiments verified that UA can induce bladder cancer cell apoptosis by regulating the PI3K/Akt signaling pathway.

Conclusions: Our study illustrated the potential mechanism of UA in bladder cancer based on network pharmacology and molecular docking. The results will provide scientific references for follow-up studies and clinical treatment.

References

Khwaza V, Oyedeji O, Aderibigbe B . Ursolic Acid-Based Derivatives as Potential Anti-Cancer Agents: An Update. Int J Mol Sci. 2020; 21(16). PMC: 7460570. DOI: 10.3390/ijms21165920. View

Balzan S, Lubrano V . LOX-1 receptor: A potential link in atherosclerosis and cancer. Life Sci. 2018; 198:79-86. DOI: 10.1016/j.lfs.2018.02.024. View

Dennis Jr G, Sherman B, Hosack D, Yang J, Gao W, Lane H . DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003; 4(5):P3. View

Bykov V, Eriksson S, Bianchi J, Wiman K . Targeting mutant p53 for efficient cancer therapy. Nat Rev Cancer. 2017; 18(2):89-102. DOI: 10.1038/nrc.2017.109. View

Motterle G, Andrews J, Morlacco A, Karnes R . Predicting Response to Neoadjuvant Chemotherapy in Bladder Cancer. Eur Urol Focus. 2019; 6(4):642-649. DOI: 10.1016/j.euf.2019.10.016. View

Allahyari M, Motavalizadeh-Kakhky A, Mehrzad J, Zhiani R, Chamani J . Cellulose nanocrystals derived from chicory plant: an un-competitive inhibitor of aromatase in breast cancer cells via PI3K/AKT/mTOP signalling pathway. J Biomol Struct Dyn. 2023; 42(11):5575-5589. DOI: 10.1080/07391102.2023.2226751. View

Liu T, Ma H, Shi W, Duan J, Wang Y, Zhang C . Inhibition of STAT3 signaling pathway by ursolic acid suppresses growth of hepatocellular carcinoma. Int J Oncol. 2017; 51(2):555-562. DOI: 10.3892/ijo.2017.4035. View

Valdes K, Morales J, Rodriguez L, Gunther G . Potential use of nanocarriers with pentacyclic triterpenes in cancer treatments. Nanomedicine (Lond). 2016; 11(23):3139-3156. DOI: 10.2217/nnm-2016-0251. View

Hou D, Liu Z, Xu X, Liu Q, Zhang X, Kong B . Increased oxidative stress mediates the antitumor effect of PARP inhibition in ovarian cancer. Redox Biol. 2018; 17:99-111. PMC: 6006521. DOI: 10.1016/j.redox.2018.03.016. View

10.

Ferreira L, Dos Santos R, Oliva G, Andricopulo A . Molecular docking and structure-based drug design strategies. Molecules. 2015; 20(7):13384-421. PMC: 6332083. DOI: 10.3390/molecules200713384. View

11.

Wozniak L, Skapska S, Marszalek K . Ursolic Acid--A Pentacyclic Triterpenoid with a Wide Spectrum of Pharmacological Activities. Molecules. 2015; 20(11):20614-41. PMC: 6332387. DOI: 10.3390/molecules201119721. View

12.

Fan Y, Ma Z, Zhao L, Wang W, Gao M, Jia X . Anti-tumor activities and mechanisms of Traditional Chinese medicines formulas: A review. Biomed Pharmacother. 2020; 132:110820. DOI: 10.1016/j.biopha.2020.110820. View

13.

Newman D, Cragg G . Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012; 75(3):311-35. PMC: 3721181. DOI: 10.1021/np200906s. View

14.

Shao J, Fang Y, Zhao R, Chen F, Yang M, Jiang J . Evolution from small molecule to nano-drug delivery systems: An emerging approach for cancer therapy of ursolic acid. Asian J Pharm Sci. 2020; 15(6):685-700. PMC: 7750806. DOI: 10.1016/j.ajps.2020.03.001. View

15.

Zang L, Wu B, Lin Y, Wang J, Fu L, Tang Z . Research progress of ursolic acid's anti-tumor actions. Chin J Integr Med. 2013; 20(1):72-9. DOI: 10.1007/s11655-013-1541-4. View

16.

Bowman T, Garcia R, Turkson J, Jove R . STATs in oncogenesis. Oncogene. 2000; 19(21):2474-88. DOI: 10.1038/sj.onc.1203527. View

17.

Lin J, Chen S, Lu C, Lin J, Yen G . Ursolic acid promotes apoptosis, autophagy, and chemosensitivity in gemcitabine-resistant human pancreatic cancer cells. Phytother Res. 2020; 34(8):2053-2066. DOI: 10.1002/ptr.6669. View

18.

Pistritto G, Trisciuoglio D, Ceci C, Garufi A, DOrazi G . Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY). 2016; 8(4):603-19. PMC: 4925817. DOI: 10.18632/aging.100934. View

19.

Jadhav N, Nadaf S, Lohar D, Ghagare P, Powar T . Phytochemicals Formulated As Nanoparticles: Inventions, Recent Patents and Future Prospects. Recent Pat Drug Deliv Formul. 2017; 11(3):173-186. DOI: 10.2174/1872211311666171120102531. View

20.

Islam M, Amin M, Siddiqui S, Hossain M, Sultana F, Kabir M . Trans fatty acids and lipid profile: A serious risk factor to cardiovascular disease, cancer and diabetes. Diabetes Metab Syndr. 2019; 13(2):1643-1647. DOI: 10.1016/j.dsx.2019.03.033. View