Evaluation of the Effects of Aminonaphthoquinone Derivatives in Combination with Curcumin Against ER-positive Breast Cancer and Related Tumours

Anticancer Res. 2017 Dec;37(12):6749-6759. doi: 10.21873/anticanres.12135.

Abstract

Background/aim: Combination therapies are often explored to treat cancer. The use of curcumin as an adjuvant to current chemotherapies has been reported, whilst aminonaphthoquinones have shown potential as anticancer agents in various tumour cell lines. This study aimed at screening synthetic aminonathoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) alone and in combination with curcumin for anti-breast cancer activity.

Materials and methods: Combination effects were determined in MCF-7 breast cancer cells using combination index analyses. Synergistic anti-proliferative effects were further investigated in breast (MCF-7, MDA-MB-231), osteosarcoma (MG-63) and endometrial (HEC-1A) cancer-derived cells.

Results: Rau 015 (15 μM) and curcumin (112.5 μM) significantly reduced MCF-7, MDA-MB-231 and MG-63 cell proliferation compared to individual treatment, indicating synergistic anti-proliferative effects. Rau 018 (30 μM) and curcumin (100 μM) displayed similar effects in MCF-7 and MG-63 cells.

Conclusion: We report on the potential of Rau 015 or Rau 018 as anti-breast cancer agents when combined with curcumin.

Keywords: Curcumin; aminonaphthoquinone; anti-estrogenic; combination.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor / methods*
  • Drug Synergism
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • MCF-7 Cells
  • Molecular Structure
  • Naphthoquinones / chemistry
  • Naphthoquinones / pharmacology*
  • Receptors, Estrogen / metabolism

Substances

  • Antineoplastic Agents
  • Insulin-Like Growth Factor Binding Protein 3
  • Naphthoquinones
  • Receptors, Estrogen
  • Alkaline Phosphatase
  • Curcumin