The Mechanism of the Synergistic Anticancer Effect of CDDP and EPA in the TE1 Cell Line

Anticancer Res. 2021 Apr;41(4):1771-1778. doi: 10.21873/anticanres.14942.

Abstract

Background/aim: Eicosapentaenoic acid (EPA) is an unsaturated fatty acid with various bioactivities, including antitumor effects. We previously reported a synergistic antitumor effect of cisplatin (CDDP) and EPA. Here, we examined the underlying mechanism.

Materials and methods: The human oesophageal cancer cell line TE-1 was treated with the combination of EPA and CDDP. Nuclear translocation of NF-κB, a transcription factor involved in cytokine production, was detected by immunohistochemistry. IL-6 levels were measured by ELISA. Apoptosis and cell cycle distribution were evaluated by flow cytometry.

Results: Nuclear translocation of NF-κB in TE-1 cells was synergistically decreased by CDDP and EPA. IL-6 production was increased following treatment with CDDP, but treatment with EPA decreased IL-6 levels. Apoptosis was synergistically induced by CDDP and EPA. A G2/M cell cycle arrest was observed with the combination of CDDP and 150 μM EPA, and S phase arrest with the combination of CDDP and 100 μM EPA.

Conclusion: The combination of CDDP and EPA synergistically suppresses NF-κB nuclear translocation and increases apoptosis by inducing cell cycle arrest at the S or G2/M phase.

Keywords: Eicosapentaenoic acid; IL-6; apoptosis; cisplatin.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Drug Synergism
  • Eicosapentaenoic Acid / pharmacology*
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Interleukin-6 / metabolism
  • NF-kappa B / metabolism
  • S Phase Cell Cycle Checkpoints / drug effects
  • Signal Transduction

Substances

  • IL6 protein, human
  • Interleukin-6
  • NF-kappa B
  • Eicosapentaenoic Acid
  • Cisplatin