Effects of acyclo-retinoic acid and lycopene on activation of the retinoic acid receptor and proliferation of mammary cancer cells

Anat Ben-Dor, Amit Nahum, Michael Danilenko, Yudith Giat, Wilhelm Stahl, Hans Dieter Martin, Theresia Emmerich, Noa Noy, Joseph Levy, Yoav Sharoni

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

The biochemical mechanisms underlying the inhibitory effects of lycopene, the main tomato carotenoid, on the growth of cancer cells are largely unknown. It has been hypothesized that lycopene derivatives may act as ligands for a nuclear receptor in analogy to retinoic acid, the hormone derived from β-carotene. The inhibition of human mammary cancer (MCF-7) cell growth and the transactivation of the retinoic acid receptor (RAR) reporter gene by synthetic acyclo-retinoic acid, the open chain analog of retinoic acid, was compared to the effects of lycopene and retinoic acid in the same systems. Acyclo-retinoic acid activated the DR-5 retinoic acid response element with a ∼100-fold lower potency than retinoic acid. This effect was independent of cotransfection with the RARα receptor. Lycopene exhibited only very modest activity in this system. In contrast to the results from the transactivation studies, acyclo-retinoic acid, retinoic acid, and lycopene inhibited cell growth with a similar potency. Preincubation with each of the three compounds slowed down cell cycle progression from G1 to S phase. In summary, acyclo-retinoic acid inhibited cancer cell growth and interacted with RAR. However, it exhibited low affinity for RAR and a correspondingly low efficacy in activating this receptor, indicating that RAR does not mediate the growth inhibitory effect of the compound. In addition, the concentrations of acyclo-retinoic acid and of lycopene required for inducing inhibition of cell growth were similar, suggesting that acyclo-retinoic acid is unlikely to be the active metabolite of lycopene.

Original languageEnglish
Pages (from-to)295-302
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume391
Issue number2
DOIs
StatePublished - 15 Jul 2001

Keywords

  • Acyclo-retinoic acid
  • Cell cycle
  • Cell growth
  • Cyclin D
  • Lycopene
  • Mammary cancer
  • Nuclear receptors
  • Retinoic acid
  • Retinoic acid receptor

Fingerprint

Dive into the research topics of 'Effects of acyclo-retinoic acid and lycopene on activation of the retinoic acid receptor and proliferation of mammary cancer cells'. Together they form a unique fingerprint.

Cite this