Archives of Pharmacal Research

, Volume 37, Issue 8, pp 1086–1095 | Cite as

Potentiation of paclitaxel activity by curcumin in human breast cancer cell by modulating apoptosis and inhibiting EGFR signaling

  • Yingzhuan Zhan
  • Yinnan Chen
  • Rui Liu
  • Han Zhang
  • Yanmin ZhangEmail author
Research Article


It has been suggested that combined effect of natural products may improve the treatment effectiveness in combating proliferation of cancer cells. Here, we examined the combined anticancer activities of compounds of three natural origin including baicalein, curcumin, and resveratrol with chemotherapy drug paclitaxel respectively, which showed that combination of paclitaxel with curcumin exhibited synergistic growth inhibition and induced significant apoptosis in MCF-7 cell lines. Treatment of MCF-7 cell lines with paclitaxel and curcumin induced the apoptosis of regulatory protein Bcl-2 but decreased Bax expression. In addition, simultaneous treatment with paclitaxel and curcumin strongly inhibited paclitaxel-induced activities of EGFR signaling. Furthermore, the combination of paclitaxel and curcumin exerted increased anti-tumor efficacy on mouse models. Overall, our data described the promising therapeutic potential and underlying mechanisms of combining paclitaxel with curcumin in treating breast cancer.


Breast cancer Paclitaxel Natural products Synergism Apoptosis EGFR signaling 



This work was supported by National Natural Science Foundation of China (Grant Nos. 81302800 and 81102414), the National Science Foundation for Post-doctoral Scientists of China (Grant No. 2013M532062).

Conflict of interest

None declared.


  1. Aggarwal, B.B. 1995. Activation of transcription factor NF-kappaB is Suppressed by curcumin (Diferuloylmethane). Journal of Biological Chemistry 270: 24995–25000.PubMedCrossRefGoogle Scholar
  2. Athar, M., J.H. Back, X. Tang, K.H. Kim, L. Kopelovich, D.R. Bickers, and A.L. Kim. 2007. Resveratrol: A review of preclinical studies for human cancer prevention. Toxicology and Applied Pharmacology 224: 274–283.PubMedCentralPubMedCrossRefGoogle Scholar
  3. Banerjee, M., P. Singh, and D. Panda. 2010. Curcumin suppresses the dynamic instability of microtubules, activates the mitotic checkpoint and induces apoptosis in MCF-7 cells. FEBS Journal 277: 3437–3448.PubMedCrossRefGoogle Scholar
  4. Chao, J.I., W.C. Su, and H.F. Liu. 2007. Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kinase and survivin associated with opposite role of p38 mitogen-activated protein kinase and AKT. Molecular Cancer Therapeutics 6: 3039–3048.PubMedCrossRefGoogle Scholar
  5. Chen, Q., S. Ganapathy, K.P. Singh, S. Shankar, and R.K. Srivastava. 2010. Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells. PLoS ONE 5: e15288.PubMedCentralPubMedCrossRefGoogle Scholar
  6. Chou, T.C., and P. Talalay. 1984. Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Advances in Enzyme Regulation 22: 27–55.PubMedCrossRefGoogle Scholar
  7. Clark, C.A., M.D. Mceachern, S.H. Shah, Y. Rong, X. Rong, C.L. Smelley, G.C. Caldito, F.W. Abreo, and C.O. Nathan. 2010. Curcumin inhibits carcinogen and nicotine-induced mammalian target of rapamycin pathway activation in head and neck squamous cell carcinoma. Cancer Prevention Research 3: 1586–1595.PubMedCrossRefGoogle Scholar
  8. Cotter, T.G. 2009. Apoptosis and cancer: The genesis of a research field. Nature Reviews Cancer 9: 501–507.PubMedCrossRefGoogle Scholar
  9. Dhillon, N., B.B. Aggarwal, R.A. Newman, R.A. Wolff, A.B. Kunnumakkara, J.L. Abbruzzese, C.S. Ng, V. Badmaev, and R. Kurzrock. 2008. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clinical Cancer Research 14: 4491–4499.PubMedCrossRefGoogle Scholar
  10. Frbmont, L. 2000. Biological effects of resveratrol. Life Sciences 66: 663–673.CrossRefGoogle Scholar
  11. Gupta, S.C., J.H. Kim, S. Prasad, and B.B. Aggarwal. 2010. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer and Metastasis Reviews 29: 405–434.PubMedCentralPubMedCrossRefGoogle Scholar
  12. Huang, W.S., Y.H. Kuo, C.C. Chin, J.Y. Wang, H.R. Yu, J.M. Sheen, S.Y. Tung, C.H. Shen, T.C. Chen, M.L. Sung, H.F. Liang, and H.C. Kuo. 2012. Proteomic analysis of the effects of baicalein on colorectal cancer cells. Proteomics 12: 810–819.PubMedCrossRefGoogle Scholar
  13. Johnson, J.J., and H. Mukhtar. 2007. Curcumin for chemoprevention of colon cancer. Cancer Letters 255: 170–181.PubMedCrossRefGoogle Scholar
  14. Li-Weber, M. 2009. New therapeutic aspects of flavones: The anticancer properties of Scutellaria and its main active constituents wogonin, baicalein and baicalin. Cancer Treatment Reviews 35: 57–68.PubMedCrossRefGoogle Scholar
  15. Maier-Lenz, H., B. Hauns, B. Haering, J. Koetting, K. Mross, C. Unger, T. Bauknecht, A. du Bois, H.G. Meerpohl, N. Hollaender, and K. Diergarten. 1997. Phase I study of paclitaxel administered as a 1-hour infusion: Toxicity and pharmacokinetics. Seminars in Oncology 24(Suppl. 19): 16–19.Google Scholar
  16. Miocinovic, R., N.P. McCabe, R.W. Keck, J. Jankun, J.A. Hampton, and S.H. Selman. 2005. In vivo and in vitro effect of baicalein on human prostate cancer cells. International Journal of Oncology 26: 241–246.PubMedGoogle Scholar
  17. Nagaraju, G.P., S. Aliya, S.F. Zafar, R. Basha, R. Diaz, and B.F. El-Rayes. 2012. The impact of curcumin on breast cancer. Integrative Biology (Cambridge) 4: 996–1007.CrossRefGoogle Scholar
  18. Newman, D.J., G.M. Cragg, and K.M. Snader. 2003. Natural products as sources of new drugs over the period 1981–2002. Journal of Natural Products 66: 1022–1037.PubMedCrossRefGoogle Scholar
  19. Nicoletti, M.I., V. Lucchini, G. Massazza, B.J. Abbott, M. D’Incalci, and R. Giavazzi. 1993. Antitumor activity of taxol (NSC-125973) in human ovarian carcinomas growing in the peritoneal cavity of nude mice. Annals of Oncology 4: 151–155.PubMedGoogle Scholar
  20. Perez, E.A. 1998. Paclitaxel in breast cancer. Oncologist 3: 373–389.PubMedGoogle Scholar
  21. Saydmohammed, M., D. Joseph, and V. Syed. 2010. Curcumin suppresses constitutive activation of STAT-3 by up-regulating protein inhibitor of activated STAT-3 (PIAS-3) in ovarian and endometrial cancer cells. Journal of Cellular Biochemistry 110: 447–456.PubMedGoogle Scholar
  22. Sharma, R.A., S.A. Euden, S.L. Platton, D.N. Cooke, A. Shafayat, H.R. Hewitt, T.H. Marczylo, B. Morgan, D. Hemingway, S.M. Plummer, M. Pirmohamed, A.J. Gescher, and W.P. Steward. 2004. Phase I clinical trial of oral curcumin: Biomarkers of systemic activity and compliance. Clinical Cancer Research 10: 6847–6854.PubMedCrossRefGoogle Scholar
  23. Shehzad, A., F. Wahid, and Y.S. Lee. 2010. Curcumin in cancer chemoprevention: Molecular targets, pharmacokinetics, bioavailability, and clinical trials. Archiv der Pharmazie 343: 489–499.PubMedCrossRefGoogle Scholar
  24. Simon, H.U., A. Haj-Yehia, and F. Levi-Schaffer. 2000. Role of reactive oxygen species (ROS). Apoptosis 5: 415–418.PubMedCrossRefGoogle Scholar
  25. Sparano, J.A., M. Wang, S. Martino, V. Jones, E.A. Perez, T. Saphner, A.C. Wolff, G.W. Sledge, W.C. Wood, and N.E. Davidson. 2008. Weekly paclitaxel in the adjuvant treatment of breast cancer. New England Journal of Medicine 358: 1663–1671.PubMedCentralPubMedCrossRefGoogle Scholar
  26. Sun, X.D., X.E. Liu, and D.S. Huang. 2012. Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression. Molecular Medicine Reports 6: 1267–1270.PubMedGoogle Scholar
  27. Takahashi, H., M.C. Chen, H. Pham, E. Angst, J.C. King, J. Park, E.Y. Brovman, H. Ishiguro, D.M. Harris, H.A. Reber, O.J. Hines, A.S. Gukovskaya, V.L. Go, and G. Eibl. 2011. Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells. Biochimica et Biophysica Acta 1813: 1465–1474.PubMedCentralPubMedCrossRefGoogle Scholar
  28. Wang, L., Y. Ling, Y. Chen, C.L. Li, F. Feng, Q.D. You, N. Lu, and Q.L. Guo. 2010. Flavonoid baicalein suppresses adhesion, migration and invasion of MDA-MB-231 human breast cancer cells. Cancer Letters 297: 42–48.PubMedCrossRefGoogle Scholar
  29. Wu, B., J. Li, D. Huang, W. Wang, Y. Chen, Y. Liao, X. Tang, H. Xie, and F. Tang. 2011. Baicalein mediates inhibition of migration. BMC Cancer 11: 527.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2013

Authors and Affiliations

  • Yingzhuan Zhan
    • 1
  • Yinnan Chen
    • 1
  • Rui Liu
    • 1
  • Han Zhang
    • 1
  • Yanmin Zhang
    • 1
    Email author
  1. 1.School of MedicineXi’an Jiaotong UniversityXi’anPeople’s Republic of China

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