In Vitro Analysis of the Combinatory Effects of Novel Aminonaphthoquinone Derivatives and Curcumin on Breast Cancer Progression

Anticancer Res. 2020 Jan;40(1):229-238. doi: 10.21873/anticanres.13944.

Abstract

Background/aim: We previously reported the potential of aminonaphthoquinone derivatives as therapeutic agents against breast and other oestrogen-responsive tumours when combined with curcumin. This study aimed at screening of novel aminonaphthoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) combined with curcumin for cytotoxic, anti-angiogenic and anti-metastatic effects on MCF-7 and MDA-MB-231 breast cancer cells.

Materials and methods: Cytotoxic and anti-angiogenic effects were analysed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and enzyme-linked immunosorbent assay; while anti-metastatic effects were measured using adhesion assay, Boyden chambers and Matrigel.

Results: Curcumin combined with Rau 008 elicited marked cytotoxic effects in MCF-7 cells compared with the individual treatments, whereas when it was combined with Rau 015 and with Rau 018, it displayed similar effects in MDA-MB-231 cells. The anti-angiogenic effect of Rau 015 plus curcumin in MCF-7 cells and Rau 018 plus curcumin in MDA-MB-231 cells was more effective than individual treatments, while the metastatic capability of MDA-MB-231 cells was significantly reduced after treatment with the aminonaphthoquinone-curcumin combinations.

Conclusion: Aminonaphthoquinones may offer significant promise as therapeutic agents against breast cancer, particularly when combined with curcumin.

Keywords: Aminonaphthoquinone; anti-angiogenic; anti-metastatic; combination; curcumin; cytotoxic.

MeSH terms

  • Breast Neoplasms / blood supply
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Disease Progression*
  • Extracellular Matrix / metabolism
  • Female
  • Humans
  • MCF-7 Cells
  • Naphthoquinones / chemistry
  • Naphthoquinones / pharmacology*
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / drug therapy
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Naphthoquinones
  • Vascular Endothelial Growth Factor A
  • Curcumin