Skip to main content

Advertisement

Log in

Investigating the therapeutic potential and mechanism of curcumin in breast cancer based on RNA sequencing and bioinformatics analysis

  • Original Article
  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Background

Breast cancer is a prevalent cancer in female. This study aims to investigate the therapeutic potential and mechanism of curcumin in breast cancer.

Methods

After cultivation, human breast cancer cells (MCF-7 cells) were treated with 0.1% (v/v) 15 µmol/ml curcumin-dimethylsulfoxide solution and 0.1% (v/v) dimethylsulfoxide, respectively, at 37 °C and 5% CO2 for 48 h. Total RNA was extracted, cDNA library was constructed, and cDNAs were amplified and sequenced. After data preprocessing, the Cufflinks software was utilized to identify differentially expressed genes (DEGs, |log2 fold change| > 0.5 and p value < 0.05). Then, functional and pathway enrichment analyses were performed through DAVID (p value < 0.05) and WebGestalt [false discovery rate (FDR) < 0.05], respectively. Furthermore, drug and disease association analyses (FDR < 0.05) were conducted through WebGestalt and DAVID, respectively. STRING was employed to construct protein–protein interaction (PPI) network (combined score > 0.4).

Results

After DEGs screening, 347 DEGs were identified. Up-regulated DEGs were enriched in 14 functions and 3 pathways, and associated with 12 drugs. Down-regulated DEGs were enriched in 14 functions and 9 pathways, and associated with 14 drugs. Moreover, 5 DEGs were associated with breast cancer, including PGAP3, MAP3K1, SERPINE1, PON2, and GSTO2. PPI network was constructed, and the top DEGs were FOS, VIM, FGF2, MAPK1, SPARC, TOMM7, PSMB10, TCEB2, SOCS1, COL4A1, UQCR11, SERPINE1, and ISG15.

Conclusion

Curcumin might have therapeutic potential in breast cancer through regulating breast cancer-related genes, including SERPINE1, PGAP3, MAP3K1, MAPK1, GSTO2, VIM, SPARC, and FGF2. However, validations are required.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.

    Article  PubMed  Google Scholar 

  2. Zilli M, Grassadonia A, Tinari N, Di Giacobbe A, Gildetti S, Giampietro J, et al. Molecular mechanisms of endocrine resistance and their implication in the therapy of breast cancer. Biochim Biophys Acta. 2009;1795:62–81.

    CAS  PubMed  Google Scholar 

  3. Baselga J, Cortés J, Kim S-B, Im S-A, Hegg R, Im Y-H, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109–19.

    Article  CAS  PubMed  Google Scholar 

  4. Basnet P, Skalko-Basnet N. Curcumin: an anti-inflammatory molecule from a curry spice on the path to cancer treatment. Molecules. 2011;16:4567–98.

    Article  CAS  PubMed  Google Scholar 

  5. Ozawa H, Imaizumi A, Sumi Y, Hashimoto T, Kanai M, Makino Y, et al. Curcumin β-d-Glucuronide plays an important role to keep high levels of free-form curcumin in the blood. Biol Pharm Bull. 2017;40:1515.

    Article  PubMed  Google Scholar 

  6. Ammon HP, Wahl MA. Pharmacology of Curcuma longa. Planta Med. 1991;57:1–7.

    Article  CAS  PubMed  Google Scholar 

  7. Choudhuri T, Pal S, Agwarwal ML, Das T, Sa G. Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Lett. 2002;512:334–40.

    Article  CAS  PubMed  Google Scholar 

  8. Nagaraju GP, Aliya S, Zafar SF, Basha R, Diaz R, El-Rayes BF. The impact of curcumin on breast cancer. Integr Biol. 2012;4:996–1007.

    Article  CAS  Google Scholar 

  9. Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7:562–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Da Wei Huang BTS, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2008;4:44–57.

    Article  Google Scholar 

  11. Wang J, Duncan D, Shi Z, Zhang B. WEB-based gene set analysis toolkit (WebGestalt): update 2013. Nucleic Acids Res. 2013;41:439.

    Google Scholar 

  12. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRING v9. 1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013;41:D808–15.

    Article  CAS  PubMed  Google Scholar 

  13. Kohl M, Wiese S, Warscheid B. Cytoscape: software for visualization and analysis of biological networks. Data mining in proteomics. Berlin: Springer; 2011. p. 291–303.

    Google Scholar 

  14. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Investig. 2011;121:2750–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Asiedu MK, Ingle JN, Behrens MD, Radisky DC, Knutson KL. TGFβ/TNFα-mediated epithelial–mesenchymal transition generates breast cancer stem cells with a claudin-low phenotype. Can Res. 2011;71:4707–19.

    Article  CAS  Google Scholar 

  16. Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, et al. The landscape of cancer genes and mutational processes in breast cancer. Nature. 2012;486:400–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhang B, Zhao Y, Zhu J. Global gene regulatory and protein interaction networks in breast cancer metastasis. Cancer Res. 2013;73:A81.

    Article  Google Scholar 

  18. Izrailit J, Berman HK, Datti A, Wrana JL, Reedijk M. High throughput kinase inhibitor screens reveal TRB3 and MAPK-ERK/TGFβ pathways as fundamental Notch regulators in breast cancer. Proc Natl Acad Sci. 2013;110:1714–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Masoudi M, Saadat I, Omidvari S, Saadat M. Association between N142D genetic polymorphism of GSTO2 and susceptibility to colorectal cancer. Mol Biol Rep. 2011;38:4309.

    Article  CAS  PubMed  Google Scholar 

  20. Wang Z, Qu K, Huang Z, Xu X, Zhang J, Zhang L, et al. Glutathione S-transferase O2 gene rs157077 polymorphism predicts response to transarterial chemoembolization in hepatocellular carcinoma. Tumor Biol. 2015;36:6463–9.

    Article  CAS  Google Scholar 

  21. Pongstaporn W, Rochanawutanon M, Wilailak S, Linasamita V, Weerakiat S, Petmitr S. Genetic alterations in chromosome 10q24. 3 and glutathione S-transferase omega 2 gene polymorphism in ovarian cancer. J Exp Clin Cancer Res CR. 2006;25:107.

    CAS  PubMed  Google Scholar 

  22. Masoudi M, Saadat I, Omidvari S, Saadat M. Additive effects of genetic variations of xenobiotic detoxification enzymes and DNA repair gene XRCC1 on the susceptibility to breast cancer. Breast Cancer Res Treat. 2010;120:263–5.

    Article  PubMed  Google Scholar 

  23. Andonova IE, Justenhoven C, Winter S, Hamann U, Baisch C, Rabstein S, et al. No evidence for glutathione S-transferases GSTA2, GSTM2, GSTO1, GSTO2, and GSTZ1 in breast cancer risk. Breast Cancer Res Treat. 2010;121:497–502.

    Article  CAS  PubMed  Google Scholar 

  24. Huang C-C, Tu S-H, Lien H-H, Jeng J-Y, Huang C-S, Huang C-J, et al. Concurrent gene signatures for han chinese breast cancers. PLoS One. 2013;8:e76421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD, et al. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res. 2011;9:997–1007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cheng C-W, Wang H-W, Chang C-W, Chu H-W, Chen C-Y, Yu J-C, et al. MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer. Breast Cancer Res Treat. 2012;134:1081–93.

    Article  CAS  PubMed  Google Scholar 

  27. Basu G, Van Vickle G, Ghazalpour A, Ashfaq R, Gatalica Z, Blevins R, et al. Frequency distribution of SPARC in triple-negative breast cancer patients. J Clin Oncol. 2011;29:s27.

    Google Scholar 

  28. Guillardoy T, Gorostiaga MA, Lanari C, Giulianelli S. FGF-2 stimulates breast cancer growth activating ER and PR. Mol Cancer Res. 2013;11:A006.

    Article  Google Scholar 

Download references

Acknowledgements

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ling Yin.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interests to state.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, R., Li, J., Zhao, Y. et al. Investigating the therapeutic potential and mechanism of curcumin in breast cancer based on RNA sequencing and bioinformatics analysis. Breast Cancer 25, 206–212 (2018). https://doi.org/10.1007/s12282-017-0816-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12282-017-0816-6

Keywords

Navigation