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Tumor Cell-selective Synergism of TRAIL- and ATRA-induced Cytotoxicity in Breast Cancer Cells

Annekathrin Reinhardt1, Hongyu Liu2, Yunxia Ma3

  • 1Department of Neuropathology, Institute for Pathology, University of Heidelberg, Heidelberg, Germany.

Anticancer Research
|May 2, 2018
PubMed
Abstract

Insights

Combining tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with all-trans retinoic acid (ATRA) synergistically inhibits breast cancer cell viability. This novel combination demonstrates tumor cell-selective cytostatic and cytotoxic effects, offering a promising alternative treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Breast cancer treatment faces challenges with pharmacoresistance.
  • Exploring novel therapeutic strategies is crucial for clinical relevance.
  • This study investigates the combined effects of TRAIL and ATRA on breast cancer cells.

Purpose of the Study:

  • To evaluate the tumor cell-inhibiting effects of combined TRAIL and ATRA.
  • To assess the selectivity of this combination therapy against breast cancer cells.
  • To elucidate the mechanisms underlying the synergistic effects.

Main Methods:

  • Utilized multiple breast cancer cell lines and a normal mammary epithelial cell line.
  • Assessed cell viability (MTT assay) and colony formation (clonogenic assay).
  • Analyzed cell death (FACS, TUNEL, ELISA), protein expression (Western blot), and receptor expression (FACS).

Main Results:

  • TRAIL and ATRA demonstrated synergistic inhibition of breast cancer cell viability.
  • Mechanisms included cytostatic and cytotoxic effects, DNA fragmentation, and enhanced caspase activity.
  • Up-regulation of TRAIL receptor and down-regulation of cyclin D1 were observed.
  • Normal mammary epithelial cells showed only slight susceptibility.

Conclusions:

  • The combination of TRAIL and ATRA exhibits potent cytostatic and cytotoxic effects.
  • These effects are selective for tumor cells, sparing normal mammary epithelial cells.
  • This combination represents a promising therapeutic approach for breast cancer treatment.
Keywords:
ATRATRAILapoptosisbreast cancercell deathretinoidssynergism

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