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Synthetic flavanones augment the anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

Ewelina Szliszka1, Edyta Kostrzewa-Susłow, Joanna Bronikowska

  • 1Department of Microbiology and Immunology, Medical University of Silesia, Katowice, Jordana 19, Zabrze 41-808, Poland.

Molecules (Basel, Switzerland)
|October 3, 2012
PubMed

Insights

Synthetic flavanones, 6-hydroxyflavanone (6-HF) and 6-propionoxy-flavanone (6-PF), enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in cancer cells. These compounds show potential for overcoming TRAIL resistance in anticancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its selective tumor cell cytotoxicity.
  • Increasing tumor cell resistance to TRAIL necessitates novel therapeutic strategies to enhance its efficacy.
  • Flavonoids are known to sensitize cancer cells to TRAIL-induced apoptosis.

Purpose of the Study:

  • To investigate the combined cytotoxic and apoptotic effects of TRAIL with synthetic flavanones 6-hydroxyflavanone (6-HF) and 6-propionoxy-flavanone (6-PF) on HeLa cancer cells.
  • To elucidate the mechanisms by which these flavanones overcome TRAIL resistance.
  • To assess the potential of flavanones in augmenting TRAIL-based anticancer therapy.

Main Methods:

  • Cytotoxicity was assessed using MTT and lactate dehydrogenase (LDH) assays.
  • Apoptosis was detected via annexin V-FITC staining using flow cytometry and microscopy.
  • Expression of death receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) and mitochondrial membrane potential (using DePsipher staining) were analyzed.

Main Results:

  • The synthetic flavanones 6-HF and 6-PF significantly enhanced TRAIL-induced apoptosis in HeLa cells.
  • Combined treatment led to increased expression of the TRAIL-R2 death receptor.
  • A reduction in mitochondrial membrane potential was observed, indicating mitochondrial pathway involvement.

Conclusions:

  • 6-HF and 6-PF augment the anticancer effects of TRAIL, offering a potential strategy to overcome TRAIL resistance.
  • These flavanones enhance TRAIL-mediated apoptosis through increased TRAIL-R2 expression and mitochondrial dysfunction.
  • The findings support the potential use of flavanones in combination with TRAIL for cancer therapy and prevention.

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