The combined effects of all-trans-retinoic acid and docosahexaenoic acid on the induction of apoptosis in human breast cancer MCF-7 cells

J Cancer Res Ther. 2016 Jan-Mar;12(1):204-8. doi: 10.4103/0973-1482.154071.


Introduction: Breast cancer is one of the most women's cancers in the worldwide. In vivo and in vitro studies showed that all-trans-retinoic acid (ATRA) and docosahexaenoic acid (DHA) can modulate differentiation and apoptosis in both cancer and immune cells. Nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) activation in the presence of their ligands, plays a critical role in the proliferation, differentiation, and apoptosis of normal cells.

Aim of study: We hypothesized that ATRA and DHA, as ligands of RARs and RXRs respectively, may have synergistic effects on the induction of apoptosis in MCF-7 human mammary carcinoma cell lines.

Materials and methods: MCF-7 cells were seeded in a 24-well plate at 3 × 105 cells per well. The cells were treated with 5 µM ATRA, 30 DHA, and various combinations of them over a 3-day trial. Apoptosis was measured by Annexin V-FITC kit and flow cytometery.

Results: Our results showed that the combination treatment of ATRA and DHA (5 µM and 30 µM and half dose at 2.5 µM and 15 µM, respectively) in a dose-dependent manner induced apoptosis rate in MCF-7 cells significantly more than single treatment of ATRA or DHA, as compared to control group (P < 0.05).

Conclusion: We conclude that the combination of ATRA and DHA at the well-balanced proportion may be effective in cancer cell apoptosis. Further studies provide details about the potential synergistically effects of combination treatment of ATRA and DHA in growth inhibition and differentiation of human mammary cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Differentiation / drug effects
  • Docosahexaenoic Acids / administration & dosage*
  • Female
  • Humans
  • MCF-7 Cells
  • Receptors, Retinoic Acid / metabolism
  • Tretinoin / administration & dosage*


  • Receptors, Retinoic Acid
  • Docosahexaenoic Acids
  • Tretinoin