PDF herunterladen
CC BY 4.0 · Pharmaceutical Fronts 2025; 07(01): e41-e52
DOI: 10.1055/a-2522-0009
Original Article

Computational Exploration of Multitarget Effects of Curcumin in Breast Cancer Treatment

Siddhartha Bethi
1   Shree P.E. (Tatya) Patil Institute of Pharmacy, Jalgaon, Maharashtra, India
,
Rahul Shirole
2   A.R.A. College of Pharmacy, Nagaon, Dhule, Maharashtra, India
,
Gauri Ghangale
3   Amrutvahini College of Pharmacy, Sangamner, Pune, Maharashtra, India
,
Subhasri Mohapatra
4   Royal College of Pharmacy, Raipur, Chhattisgarh, India
,
Asmita Gaikwad
5   Sharadchandra Pawar College of Pharmacy, Otur, Pune, Maharashtra, India
,
Harshal Tare
5   Sharadchandra Pawar College of Pharmacy, Otur, Pune, Maharashtra, India
› Institutsangaben Funding None.
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

Abstract

Curcumin, a bioactive compound derived from Curcuma longa, has shown promising potential in breast cancer therapy due to its multitarget pharmacological effects. This study aimed to explore the molecular mechanisms underlying curcumin's anticancer activity using an integrative computational approach, including predictive modeling, molecular docking, and pathway enrichment analysis. Curcumin demonstrated strong binding affinities to critical targets such as matrix metalloproteinase-9 (MMP9), protein kinase B (AKT1), epidermal growth factor receptor (EGFR), and signal transducer and activator of transcription 3 (STAT3), which are implicated in pathways regulating cancer cell survival, proliferation, invasion, and metastasis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed curcumin's ability to modulate processes like apoptosis, inflammation, and cell signaling, emphasizing its therapeutic versatility. Molecular docking and dynamics simulations further validated its stable interactions with key targets. Complementing the computational findings, in vitro studies using MCF-7 breast cancer cells confirmed curcumin's dose-dependent cytotoxic effects. These results highlight curcumin's potential as a complementary therapeutic agent in breast cancer management, and in vivo studies are needed to substantiate its clinical utility in further studies.

Keywords

curcumin - breast cancer - molecular docking - pathway analysis


Publikationsverlauf

Eingereicht: 20. September 2024

Angenommen: 21. Januar 2025

Artikel online veröffentlicht:
03. März 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Lemij AA, Bastiaannet E, De Glas NA. et al. Breast cancer in the older population: a global challenge—an epidemiological perspective. Ann Breast Surg 2023; 7: 17
    CrossrefSuche in Google Scholar
  • 2 Shang C, Xu D. Epidemiology of breast cancer. Oncologie 2022; 24 (04) 649-663
    CrossrefSuche in Google Scholar
  • 3 Smolarz B, Nowak AZ, Romanowicz H. Breast cancer—epidemiology, classification, pathogenesis and treatment (review of literature). Cancers (Basel) 2022; 14 (10) 2569
    CrossrefPubMedSuche in Google Scholar
  • 4 Iacopetta D, Ceramella J, Baldino N, Sinicropi MS, Catalano A. Targeting breast cancer: an overlook on current strategies. Int J Mol Sci 2023; 24 (04) 3643
    CrossrefPubMedSuche in Google Scholar
  • 5 Swaminathan H, Saravanamurali K, Yadav SA. Extensive review on breast cancer its etiology, progression, prognostic markers, and treatment. Med Oncol 2023; 40 (08) 238
    CrossrefPubMedSuche in Google Scholar
  • 6 Fuloria S, Mehta J, Chandel A. et al. A comprehensive review on the therapeutic potential of Curcuma longa Linn. in relation to its major active constituent curcumin. Front Pharmacol 2022; 13: 820806
    CrossrefPubMedSuche in Google Scholar
  • 7 Jyotirmayee B, Mahalik G. A review on selected pharmacological activities of Curcuma longa L. Int J Food Prop 2022; 25 (01) 1377-1398
    CrossrefSuche in Google Scholar
  • 8 Song X, Zhang M, Dai E, Luo Y. Molecular targets of curcumin in breast cancer (review). Mol Med Rep 2019; 19 (01) 23-29
    PubMedSuche in Google Scholar
  • 9 Shahbaz M, Imran M, Hussain M. et al. Curcumin: a bioactive compound with molecular targets for human malignancies. Food Agric Immunol 2023; 34 (01) 2280524
    CrossrefSuche in Google Scholar
  • 10 Cacciola NA, Cuciniello R, Petillo GD, Piccioni M, Filosa S, Crispi S. An overview of the enhanced effects of curcumin and chemotherapeutic agents in combined cancer treatments. Int J Mol Sci 2023; 24 (16) 12587
    CrossrefPubMedSuche in Google Scholar
  • 11 Yang ZJ, Huang SY, Zhou DD. et al. Effects and mechanisms of curcumin for the prevention and management of cancers: an updated review. Antioxidants 2022; 11 (08) 1481
    CrossrefPubMedSuche in Google Scholar
  • 12 Shen H, Shen J, Pan H. et al. Curcumin analog B14 has high bioavailability and enhances the effect of anti-breast cancer cells in vitro and in vivo . Cancer Sci 2021; 112 (02) 815-827
    CrossrefPubMedSuche in Google Scholar
  • 13 Barcelos KA, Mendonça CR, Noll M, Botelho AF, Francischini CRD, Silva MAM. Antitumor properties of curcumin in breast cancer based on preclinical studies: a systematic review. Cancers (Basel) 2022; 14 (09) 2165
    CrossrefPubMedSuche in Google Scholar
  • 14 Somers-Edgar TJ, Scandlyn MJ, Stuart EC, Le Nedelec MJ, Valentine SP, Rosengren RJ. The combination of epigallocatechin gallate and curcumin suppresses ER α-breast cancer cell growth in vitro and in vivo . Int J Cancer 2008; 122 (09) 1966-1971
    CrossrefPubMedSuche in Google Scholar
  • 15 Mishra AP, Swetanshu Singh P. et al. Role of the dietary phytochemical curcumin in targeting cancer cell signalling pathways. Plants 2023; 12 (09) 1782
    CrossrefPubMedSuche in Google Scholar
  • 16 Noor F, Tahir Ul Qamar M, Ashfaq UA, Albutti A, Alwashmi ASS, Aljasir MA. Network pharmacology approach for medicinal plants: review and assessment. Pharmaceuticals (Basel) 2022; 15 (05) 572
    CrossrefPubMedSuche in Google Scholar
  • 17 Noor F, Rehman A, Ashfaq UA. et al. Integrating network pharmacology and molecular docking approaches to decipher the multi-target pharmacological mechanism of Abrus precatorius L. acting on diabetes. Pharmaceuticals (Basel) 2022; 15 (04) 414
    CrossrefPubMedSuche in Google Scholar
  • 18 Ferrari IV, De Gregorio A, Fuggetta MP, Ravagnan G. PharmMapper server and molecular docking study focusing on polydatin to identify potential targets. Eur J Appl Sci 2023; 11 (05) 163-167
    Suche in Google Scholar
  • 19 Yan L, Zhang Z, Liu Y. et al. Anticancer activity of erianin: cancer-specific target prediction based on network pharmacology. Front Mol Biosci 2022; 9: 862932
    CrossrefPubMedSuche in Google Scholar
  • 20 Luo Y, Fu Y, Tan T. et al. Screening of lncRNA-miRNA-mRNA coexpression regulatory networks involved in acute traumatic coagulation dysfunction based on CTD, GeneCards, and PharmGKB Databases. Oxid Med Cell Longev 2022; 2022 (01) 7280312
    PubMedSuche in Google Scholar
  • 21 Davis AP, Wiegers TC, Johnson RJ, Sciaky D, Wiegers J, Mattingly CJ. Comparative toxicogenomics database (CTD): update 2023. Nucleic Acids Res 2023; 51 (D1): D1257-D1262
    CrossrefPubMedSuche in Google Scholar
  • 22 Wang Y, Lao Y, Li R. et al. Network pharmacological analysis and experimental study of melatonin in chronic prostatitis/chronic pelvic pain syndrome. Naunyn Schmiedebergs Arch Pharmacol 2024; 397 (11) 8691-8706
    CrossrefPubMedSuche in Google Scholar
  • 23 Zu G, Sun K, Li L, Zu X, Han T, Huang H. Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus. Sci Rep 2021; 11 (01) 22959
    CrossrefPubMedSuche in Google Scholar
  • 24 Gong L, Whirl-Carrillo M, Klein TE. PharmGKB, an integrated resource of pharmacogenomic knowledge. Curr Protoc 2021; 1 (08) e226
    CrossrefPubMedSuche in Google Scholar
  • 25 He Q, Liu C, Wang X. et al. Exploring the mechanism of curcumin in the treatment of colon cancer based on network pharmacology and molecular docking. Front Pharmacol 2023; 14: 1102581
    CrossrefPubMedSuche in Google Scholar
  • 26 Wimalagunasekara SS, Weeraman JWJK, Tirimanne S, Fernando PC. Protein-protein interaction (PPI) network analysis reveals important hub proteins and sub-network modules for root development in rice (Oryza sativa). J Genet Eng Biotechnol 2023; 21 (01) 69
    CrossrefPubMedSuche in Google Scholar
  • 27 Wu Z, Yang T, Ma H. Molecular mechanism of modified Huanglian Wendan decoction in the treatment of polycystic ovary syndrome. Medicine (Baltimore) 2023; 102 (15) e33212
    CrossrefPubMedSuche in Google Scholar
  • 28 Sherman BT, Hao M, Qiu J. et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res 2022; 50 (W1): W216-W221
    CrossrefPubMedSuche in Google Scholar
  • 29 Wakale V, Kachave R, Gholap P, Mahajan K, Tare H. Design and discovery of genistein-based drugs as a potential tyrosine kinase inhibitor for lung adenocarcinoma through hybrid in silico methods. International Journal of Drug Delivery Technology 2023; 13 (04) 1422-1427
    CrossrefSuche in Google Scholar
  • 30 Deore S, Kachave R, Gholap P, Mahajan K, Tare H. Computational identification of methionyl-tRNA-synthetase inhibitors for Brucella melitensis: a hybrid of ligand-based classic 3-point pharmacophore screening and structure cavity guided blind docking approach. Int J Pharm Qual Assurance 2023; 14 (04) 1151-1157
    CrossrefSuche in Google Scholar
  • 31 Tajane P, Kayande N, Bhosale A, Deore S, Tare H. Design and discovery of silmitasertib-based drugs as a potential casein kinase II inhibitor for cholangiocarcinoma through hybrid in-silico ligand-based virtual screening with molecular docking method. Int J Drug Deliv Technol 2023; 13 (04) 1514-1519
    CrossrefSuche in Google Scholar
  • 32 Tare H, Vaidya V, Fulmali S, Jadhao S, Wankhade M, Bhise M. Transcriptomic insight and structural integration: repositioning FDA-approved methotrexate derivative for precision therapy in lung cancer through drug-drug similarity analysis and cavity-guided blind docking. Int Res J Multidisciplinary Scope 2024; 5 (01) 631-639
    CrossrefSuche in Google Scholar
  • 33 Mujawar T, Tare H, Deshmukh N, Udugade B, Thube U. Repurposing FDA-approved anastrozole-based drugs for breast cancer through drug-drug transcriptomic similarity and cavity detection guided blind docking. Int J Drug Deliv Technol 2023; 13 (04) 1172-1177
    CrossrefSuche in Google Scholar
  • 34 Gaikwad A, Kayande N, Tare H, Udugade B, Kachave R. In silico design and development of multi-target agents targeting glycogen synthase kinase-3 beta and vascular endothelial growth factor receptor 2 for acute myeloid leukemia. Int J Drug Deliv Technol 2023; 13 (04) 1428-1434
    CrossrefSuche in Google Scholar
  • 35 Tare H, Thube U, Kachave R, Wagh V, Udugade B. Catechins as catalase modulators: a comprehensive in silico analysis unveiling their potential antioxidant effects. Int J Drug Deliv Technol 2023; 13 (04) 1156-1160
    CrossrefSuche in Google Scholar
  • 36 Raman APS, Kumari K, Jain P. et al. In Silico evaluation of binding of 2-deoxy-D-glucose with Mpro of nCoV to combat COVID-19. Pharmaceutics 2022; 14 (01) 135
    CrossrefPubMedSuche in Google Scholar
  • 37 Wishart DS, Tian S, Allen D. et al. BioTransformer 3.0-a web server for accurately predicting metabolic transformation products. Nucleic Acids Res 2022; 50 (W1): W115-W123
    CrossrefPubMedSuche in Google Scholar
  • 38 Senthilraja P, Kathiresan KJ. In vitro cytotoxicity MTT assay in Vero, HepG2 and MCF-7 cell lines study of Marine Yeast. J Appl Pharm Sci 2015; 5 (03) 80-84
    CrossrefSuche in Google Scholar
  • 39 Tan T, Li S, Hu W. et al. Efficacy and safety of nab-paclitaxel plus platinum in non-small cell lung cancer: a meta-analysis. Front Med (Lausanne) 2023; 10: 1139248
    CrossrefPubMedSuche in Google Scholar
  • 40 Talakesh T, Tabatabaee N, Atoof F. et al. Effect of nano-curcumin on radiotherapy-induced skin reaction in breast cancer patients: a randomized, triple-blind, placebo-controlled trial. Curr Radiopharm 2022; 15 (04) 332-340
    CrossrefPubMedSuche in Google Scholar