Synergistic Interaction between 5-FU and an Analog of Sulforaphane-2-Oxohexyl Isothiocyanate-In an In Vitro Colon Cancer Model

Molecules. 2021 May 19;26(10):3019. doi: 10.3390/molecules26103019.

Abstract

Combination therapy is based on the beneficial effects of pharmacodynamic interaction (synergistic or additive) between combined drugs or substances. A considerable group of candidates for combined treatments are natural compounds (e.g., isothiocyanates) and their analogs, which are tested in combination with anticancer drugs. We tested the anticancer effect of the combined treatment of isothiocyanate 2-oxohexyl isothiocyanate and 5-fluorouracil in colon and prostate cancer cell lines. The type of interaction was described using the Chou-Talalay method. The cytostatic and cytotoxic activities of the most promising combined treatments were investigated. In conclusion, we showed that combined treatment with 5-fluorouracil and 2-oxohexyl isothiocyanate acted synergistically in colon cancer. This activity is dependent on the cytostatic properties of the tested compounds and leads to the intensification of their individual cytotoxic activity. The apoptotic process is considered to be the main mechanism of cytotoxicity in this combined treatment.

Keywords: 5-fluorouracil; isothiocyanates; sulforaphane; synergistic effect.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / pathology*
  • Drug Synergism
  • Fluorouracil / pharmacology*
  • Humans
  • In Vitro Techniques
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology*
  • Models, Biological
  • Sulfoxides / chemistry
  • Sulfoxides / pharmacology*
  • Thiocyanates / chemistry
  • Thiocyanates / pharmacology*

Substances

  • 2-oxohexyl isothiocyanate
  • Antineoplastic Agents
  • Isothiocyanates
  • Sulfoxides
  • Thiocyanates
  • sulforaphane
  • Fluorouracil