3 years ago

The highly bioactive molecule and signal substance 6-formylindolo[3,2- b ]carbazole (FICZ) plays bi-functional roles in cell growth and apoptosis in vitro

Afshin Mohammadi-Bardbori, Amin-Reza Akbarizadeh, Farzaneh Bastan


The maintenance of cellular homeostasis is a complex process that is governed by the receipt of prototypical growth and death signals. The endogenous functions of aryl hydrocarbon receptor (AHR) in cellular homeostasis are not well understood. We aimed to establish whether the disturbance of endogenously activated AHR can influence cell growth, and if so, what mechanism(s) are involved. Cell growth was measured in mouse hepatoma Hepa-1 wild-type and cytochrome P4501A1 (CYP1A1)-deficient c37 cells. In other sets of experiments, HepG2 cells were exposed to different doses of FICZ (0.01nM–1 µM) alone or in combination with 50 nM of the CYP1A1 inhibitor 3′methoxy-4′nitro-flavone (MNF). CYP1A1 enzyme activity, cell viability, oxidative stress, and several endpoints of apoptosis were measured. FICZ treatment at a high concentration or in combination with MNF induced sustained CYP1A1 activity and led to oxidative stress and activation of apoptosis via a mitochondrial-dependent pathway. In comparison with the wild-type Hepa-1 cells, c37 cells lacking CYP1A1 activity proliferated faster in normal medium which contains trace levels of FICZ. Besides, in HepG2 cells, FICZ stimulated cell growth at low concentrations but inhibited cell growth at high concentrations. Based on these findings, we propose that CYP1A1 inhibitors, by increasing the levels of the endogenous ligand FICZ, change the cell growth kinetics and trigger cell death and apoptosis through a mitochondrial-dependent pathway. Since AHR controls multiple cellular functions, a wide range of toxicity can be expected by disturbing its endogenous functions.

Publisher URL: https://link.springer.com/article/10.1007/s00204-017-1950-9

DOI: 10.1007/s00204-017-1950-9

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.