Curcumin suppresses doxorubicin-induced epithelial-mesenchymal transition via the inhibition of TGF-β and PI3K/AKT signaling pathways in triple-negative breast cancer cells

J Agric Food Chem. 2013 Dec 4;61(48):11817-24. doi: 10.1021/jf404092f. Epub 2013 Nov 21.

Abstract

Triple-negative breast cancer (TNBC) is defined by a lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER 2). Therefore, targeted therapy agents may not be used, and therapy is largely limited to chemotherapy. Doxorubicin treatment consequently acquires undesired malignance characteristics [i.e., epithelial-mesenchymal transition (EMT) and multi-drug resistance]. Our results illustrated that doxorubicin triggered EMT and resulted in the acquisition of a mesenchymal phenotype in TNBC cells. Moreover, we found that transforming growth factor-β (TGF-β) and PI3K/AKT signaling pathways were acquired for doxorubicin-induced EMT. Interestingly, we found that curcumin suppressed doxorubicin-induced EMT. Curcumin reversed doxorubicin-induced morphological changes, inhibited doxorubicin-induced downregulation of E-cadherin expressions, and inhibited doxorubicin-induced upregulation of vimentin expression. We also found that curcumin inhibited doxorubicin-induced EMT by inhibiting the TGF-β and PI3K/AKT signaling pathways. Moreover, curcumin enhanced the antiproliferative effects of doxorubicin in TNBC cells. In summary, our results suggest that doxorubicin in combination with curcumin may be a potential therapy for TNBC.

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / physiopathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Curcumin / pharmacology*
  • Down-Regulation / drug effects
  • Doxorubicin / pharmacology*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Female
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta / metabolism*

Substances

  • Transforming Growth Factor beta
  • Doxorubicin
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Curcumin