Study on the mechanism of Curcuma zedoaria in breast cancer based on network pharmacology

Abstract

This study explored the anti-breast cancer (BC) mechanism of Curcuma zedoaria (CZ) via the network pharmacology approach. The active components of CZ were screened by oral bioavailability (OB) and drug-likeness (DL) criteria using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The potential targets of CZ were predicted through TCMSP and SwissTargetPrediction, while BC-related target genes were screened via GeneCards and the Online Mendelian Inheritance in Man (OMIM) database. The common target genes of CZ and BC were obtained by using the Venn tool. The protein interaction network diagram was constructed by using String software. The network diagram of CZ components was created by using Cytoscape 3.8.0. The intersection genes of drugs and diseases were analyzed by using the R language software for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Finally, the docking activity between the active ingredient and the key target was verified through molecular docking. Through the methods of database search and literature mining, 23 bio-active components of CZ and 370 corresponding gene targets, 1776 disease gene targets, and 132 drug-disease intersection genes were obtained. GO analysis revealed 67 types of cellular components, 113 molecular functions, and 2042 biological processes. KEGG analysis identified 138 enriched pathways. This study preliminarily elucidated the potential mechanism underlying the therapeutic effect of CZ on BC.

Keywords

Curcuma zedoaria (CZ) / breast cancer (BC) / network pharmacology / mechanism of action

References

[1] Yue GG, Wong LS, Leung HW, et al. Evaluation of the safety profiles of estrogenic Chinese herbal medicines in breast cancer. Phytoimedcine, 2019, 56: 103-17.

[2] Hou Y, Wang J, Bao H, et al. Study on the mechanism of zedoary turmeric oil combined with docetaxel in the treatment of breast cancer based on network pharmacology and molecular docking technology. Asian J Tradit Med, 2025, 20: 271-84.

[3] Xu X, Yang J, Zhou W, et al. Genetic variations within alternative splicing associated genes are associated with breast cancer susceptibility in Chinese women. Gene, 2019, 706: 140-5.

[4] Zagouri F, Liakou P, Bartsch R, et al. Discrepancies between ESMO and NCCN breast cancer guidelines: An appraisal. Breast, 2015, 24: 513-23.

[5] Huang WT, Hung HH, Kao YW, et al. Application of neural network and cluster analyses to differentiate TCM patterns in patients with breast cancer. Front Pharmacol, 2020, 11: 670.

[6] Ou J, Zhu X, Zhang X, et al. A retrospective study of curcumin in combination with intravenous vitamin C (IVC) on triple negative breast cancer (TNBC). J Clin Oncol, 2018, 36: e13118.

[7] Alsaikhan F. The synergistic effect of resveratrol and curcumin on oncogenic lncRNA MAPT-IT1 and ferroptosis-related genes in breast cancer. Naunyn Schmiedebergs Arch Pharmacol, 2026, 399: 1091-108.

[8] Li Y, Sun XY, Lin CY, et al. Chemical constituents of essential oil from C.Phaeocaulis, C.kwangsinensis, and C.wenyujin. Chin Tradit Herb Drugs, 2005, 35: 1785-7.

[9] Ning L, Ma H, Jiang Z, et al. Curcumol suppresses breast cancer cell metastasis by inhibiting MMP-9 via JNK1/2 and Akt-dependent NF-κB signaling pathways. Integr Cancer Ther, 2016, 15: 216-25.

[10] Song AL, Li JW, Shi GX. Study on the intervention of curcuma oil on cell proliferation and expression of apoptosis factors in rat cells with breast cancer precancerous lesions. Proc 15th Natl Acad Exch Conf Integr Tradit Chin West Med Otolaryngol, 2011, Zhangjiajie, China, 5.

[11] Wang YH. Systems pharmacology-based research framework of traditional Chinese medicine. Proc 12th Natl Symp Tradit Chin Med Nat Med, 2012, Haikou, China, 1.

[12] Yuan J, Hu J, He H, et al. Research progress on network pharmacology in traditional Chinese medicine. Hainan Med J, 2020, 31: 2688-91.

[13] Pan Y, Wang W, Huang S, et al. Beta-elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation. J Cell Mol Med, 2019, 23: 6846-58.

[14] Wang Y, Yu J, Cui R, et al. Curcumin in treating breast cancer: A review. J Lab Autom, 2016, 21: 723-31.

[15] Zhong Z, Chen X, Tan W, et al. Germacrone inhibits the proliferation of breast cancer cell lines by inducing cell cycle arrest and promoting apoptosis. Eur J Pharmacol, 2011, 667: 50-55.

[16] Li J, Bian WH, Wan J, et al. Curdione inhibits proliferation of MCF-7 cells by inducing apoptosis. Asian Pac J Cancer Prev, 2014, 15: 9997-10001.

[17] Zhao C, She T, Wang L, et al. Daucosterol inhibits cancer cell proliferation by inducing autophagy through reactive oxygen species-dependent manner. Life Sci, 2015, 137: 37-43.

[18] Shieh JM, Chen YC, Lin YC, et al. Demethoxycurcumin inhibits energy metabolic and oncogenic signaling pathways through AMPK activation in triple-negative breast cancer cells. J Agric Food Chem, 2013, 61: 6366- 75.

[19] Wang Z. Virtual simulation experiment based on MOE software - Molecular docking of donepezil and acetylcholinesterase. Chem Educ, 2022, 43: 107-11.

[20] Li S. Framework and practice of network-based studies for Chinese herbal formula. Chin J Integr Med, 2007, 489-93.

[21] Riggio M, Perrone MC, Polo ML, et al. AKT1 and AKT2 isoforms play distinct roles during breast cancer progression through the regulation of specific downstream proteins. Sci Rep, 2017, 7: 44244.

[22] Rudolph M, Anzeneder T, Schulz A, et al. AKT 1 (E17K) mutation profiling in breast cancer: prevalence, concurrent oncogenic alterations, and blood-based detection. BMC Cancer, 2016, 16: 622.

[23] Hinz N, Jücker M. Distinct functions of AKT isoforms in breast cancer: a comprehensive review. Cell Commun Signal, 2019, 17: 154.

[24] Bao C, Chen J, Chen D, et al. MiR-93 suppresses tumorigenesis and enhances chemosensitivity of breast cancer via dual targeting E2F1 and CCND1. Cell Death Dis, 2020, 11: 618.

[25] Bemanian V, Sauer T, Touma J, et al. The epidermal growth factor receptor (EGFR/HER-1) gatekeeper mutation T790M is present in European patients with early breast cancer. PLoS One, 2015, 10: e134398.

[26] Jura N, Zhang X, Endres NF, et al. Catalytic control in the EGF receptor and its connection to general kinase regulatory mechanisms. Mol Cell, 2011, 42: 9-22.

[27] Dragowska WH, Weppler SA, Wang JC, et al. Induction of autophagy is an early response to gefitinib and a potential therapeutic target in breast cancer. PLoS One, 2013, 8: e76503.

[28] Heo TH, Wahler J, Suh N. Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer. Oncotarget, 2016, 7: 15460-73.

[29] Yu K, Toral-Barza L, Discafani C, et al. mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr Relat Cancer, 2001, 8: 249-58.

[30] Asiaf A, Ahmad ST, Arjumand W, et al. MicroRNAs in breast cancer: diagnostic and therapeutic potential. Methods Mol Biol, 2018, 1699: 23-43.

[31] Zhang G, Liu Z, Xu H, et al. miR-409-3p suppresses breast cancer cell growth and invasion by targeting Akt1. Biochem Biophys Res Commun, 2016, 469: 189-95.

[32] Deng X, Zhao Y, Wang B. miR-519d-mediated downregulation of STAT3 suppresses breast cancer progression. Oncol Rep, 2015, 34: 2188-94.

[33] Zhao SX, Wang T, Li YJ. The role of miR-21 in human breast cancer MCF-7 cells invasion by regulating STAT3 expression. Chin J Clin Pathol, 2016, 8: 5-9.

[34] Sun XR, Yang K, Lu LL, et al. Effect and mechanism of curdione on migration and invasion of breast cancer HCC 1937 cells. Chin J Exp Tradit Med Formulae, 2019, 25: 66-73.