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

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Year: 2019
COI code: TOXICOLOGY15_188
Paper Language: English

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

  Afshin Mohammadi-Bardbori - Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
  Farzaneh Bastan - Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
  Amin-Reza Akbarizadeh - Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract:

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 cellular homeostasis and, if so, what mechanism(s) are involved.Mouse hepatoma Hepa-1 wild type and cytochrome P450 1A1 (CYP1A1) deficient c37 cells were treated in a medium which was not contaminated with background levels of FICZ. In other sets of experiments, HepG2 cells were exposed to different doses of FICZ (1nM to 1μM) alone or in combination with 10nM of the 3’methoxy-4’nitroflavone (MNF). CYP1A1 enzyme activity, cell viability, oxidative stress and several endpoints of apoptosis were measured.A sustained induction of CYP1A1 enzyme activity was seen with either high concentrations or low concentrations of FICZ in combination with MNF. FICZ treatment at a high concentration or in combination with MNF led to activation of apoptosis via mitochondrial-dependent pathway. In comparison with the wild type Hepa-1 cells, c37 cells showed a higher rate of cell growth. Besides, in HepG2 cells, FICZ showed a hormetic effect on cell viability.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 apoptosis through a mitochondrial-dependent pathway.Since AHR controls the network of proteins, a wide range of toxicity can be expected by disturbing endogenous AHR functions.

Keywords:

6-formylindolo [3, 2-b] carbazole (FICZ); cell growth; apoptosis; mitochondrial-dependent pathway

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Mohammadi-Bardbori, Afshin; Farzaneh Bastan & Amin-Reza Akbarizadeh, 2019, The highly bioactive molecule and signal substance, 6-formylindolo [3, 2-b] carbazole (FICZ) plays bi-functional role in cell growth and apoptosis in vitro, 15th iranian congress of toxicology, تهران, دانشگاه علوم پزشكي شهيد بهشتي, https://www.civilica.com/Paper-TOXICOLOGY15-TOXICOLOGY15_188.htmlInside the text, wherever referred to or an achievement of this article is mentioned, after mentioning the article, inside the parental, the following specifications are written.
First Time: (Mohammadi-Bardbori, Afshin; Farzaneh Bastan & Amin-Reza Akbarizadeh, 2019)
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Type: Medical University
Paper No.: 2097
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