Modulation of Tamoxifen Cytotoxicity by Caffeic Acid Phenethyl Ester in MCF-7 Breast Cancer Cells

Oxid Med Cell Longev. 2016;2016:3017108. doi: 10.1155/2016/3017108. Epub 2015 Nov 30.

Abstract

Although Tamoxifen (TAM) is one of the most widely used drugs in managing breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a polyphenolic compound present in many medicinal plants and in propolis. The present study examined the effect of CAPE on TAM cytotoxicity in MCF-7 cells. MCF-7 cells were treated with different concentrations of TAM and/or CAPE for 48 h. This novel combination exerted synergistic cytotoxic effects against MCF-7 cells via induction of apoptotic machinery with activation of caspases and DNA fragmentation, along with downregulation of Bcl-2 and Beclin 1 expression levels. However, the mammalian microtubule-associated protein light chain LC 3-II level was unchanged. Vascular endothelial growth factor level was also decreased, whereas levels of glutathione and nitric oxide were increased. In conclusion, CAPE augmented TAM cytotoxicity via multiple mechanisms, providing a novel therapeutic approach for breast cancer treatment that can overcome resistance and lower toxicity. This effect provides a rationale for further investigation of this combination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis Regulatory Proteins / metabolism
  • Beclin-1
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Caffeic Acids / pharmacology
  • Female
  • Humans
  • MCF-7 Cells
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Phenylethyl Alcohol / analogs & derivatives
  • Phenylethyl Alcohol / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tamoxifen / pharmacology

Substances

  • Apoptosis Regulatory Proteins
  • BCL2 protein, human
  • BECN1 protein, human
  • Beclin-1
  • Caffeic Acids
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • light chain 3, human
  • Tamoxifen
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol