Cytotoxicity of juglone and thymoquinone against pancreatic cancer cells

Chem Biol Interact. 2020 Aug 25:327:109142. doi: 10.1016/j.cbi.2020.109142. Epub 2020 Jun 28.

Abstract

Juglone and thymoquinone are cytotoxic to pancreatic cancer cells. The aim of this study was to investigate, using an analysis of isobolograms, the type and degree of interactions between juglone and thymoquinone on MIA PaCa-2 pancreatic cancer cells. Cell viability was evaluated using the MTT assay. Cell death was determined by flow cytometry. The IC50 value for juglone and TQ in combination was found to be 24.75 μM, which was higher than juglone or TQ alone. Juglone alone killed Mia Paca-2 cells by ferroptosis. At concentrations where 10, 20 or 50% of cells were affected, there existed a moderate antagonistic relationship between juglone and TQ as indicated by the combination index (CI) value determined by the Compusyn software. At concentrations that affected 75% and 90% of cells, there were nearly an additive effect with CI value of 1.09249 and 0.92391, respectively. Moderate synergism was only seen at concentration where 95% of cells were affected, and the corresponding concentration of juglone and TQ at that combination was 40.90 μM and 511.19 μM, respectively.

Keywords: Combinatorial index; Isobologram; Juglone; Pancreatic cancer; Thymoquinone.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzoquinones / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Humans
  • Naphthoquinones / pharmacology*
  • Pancreatic Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • Naphthoquinones
  • thymoquinone
  • juglone