Effects of Curcumin Analogues DMC and EF24 in Combination with the Cytokine TRAIL against Kidney Cancer

Molecules. 2021 Oct 18;26(20):6302. doi: 10.3390/molecules26206302.

Abstract

The natural compound curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma (RCC) cells when combined with TNF-related apoptosis-inducing ligand (TRAIL), a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, the therapeutic effects of curcumin are limited by its low bioavailability. Similar compounds to curcumin with higher bioavailability, such as demethoxycurcumin (DMC) and 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), can potentially have similar anticancer effects and show a similar synergy with TRAIL, thus reducing RCC viability. This study aims to show the effects of DMC and EF24 in combination with TRAIL at reducing ACHN cell viability and ACHN cell migration. It also shows the changes in death receptor 4 (DR4) expression after treatment with these compounds individually and in combination with TRAIL, which can play a role in their mechanism of action.

Keywords: DMC; EF24; TRAIL; curcumin; kidney cancer.

MeSH terms

  • Apoptosis
  • Benzylidene Compounds / pharmacology*
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Movement
  • Diarylheptanoids / pharmacology*
  • Drug Therapy, Combination
  • Humans
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Piperidones / pharmacology*
  • TNF-Related Apoptosis-Inducing Ligand / administration & dosage*
  • Tumor Cells, Cultured

Substances

  • 3,5-bis(2-fluorobenzylidene)piperidin-4-one
  • Benzylidene Compounds
  • Diarylheptanoids
  • Piperidones
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • demethoxycurcumin