Keloids are bening fibroproliferative tumors considered to be scars that results when wounds heal abnormally. The underlaying pathophysilogical mechanism is unclear. However disturbed cell cycle regulation is observed in keloids. The process plays an important role in maintaining genetic integrity of the cell. P53 can arrest human cells with damaged DNA in G1 phase of cell cycle, that allows DNA repair before S-phase. If the DNA damage is severe and cannot be repaired, apoptotic pathways are activated to eliminate damaged cells. P53 as a transactivator of transcription can induce apoptosis by up-regulation of pro-apoptotic gene expression such as BAX and down-regulation of antiapoptotic genes expression such as BCL-2.

Genistein (4,5,7-trihydroxyisoflavone) exhibits multidirectional biological action. The concentration of genistein is relatively high in soybean. Genistein has been shown as effective antioxidant and chemopreventive agent. Genistein can  bind to estrogen receptors (ERs) and modulate estrogen action due to its structure similarity to human estrogens. Genistein also inhibits transcription factors NFΚB, Akt and AP-1 signaling pathways, that are important for cell proliferation, differentiation, survival and apoptosis.

The aim of the study was to investigate genistein as a potential regulator of  TP53, CDKN1A, BAX and BCL-2  in normal fibroblasts and fibroblasts derived from keloids cultured in vitro.

Natural soybean genistein in: 370 µM, 185 µM, 92,5 µM, 37µM, 18,5 µM, 3,7 µM, 1,85 µM and 0,185 µM concentrations were used in the study. Real time RT-QPCR was used to estimate transcription level of selected genes in normal and keloid fibroblasts treated with genistein.

Results: TP53 and CDKN1A genes expression are modulated by genistein in concentration dependent manner. The agent also modulates BAX/BCL-2  ratio in examined cells.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/31085 must be provided.

1. The transcripional activity of genes encoding MMPs and TIMPs in breast cancer cells treated by genistein and in normal cancer-associated fibroblasts - in vitro studies
2. Molecular effects of newly synthesized derivatives of phenothiazine in C-32 and MDA-MD-231 cancer cells
3. Evaluation of genistein ability to modulate the protein expression of CTGF and the genes expression of TGF β1, β2 and β3 isoforms in keloid fibroblasts in vitro
4. Effect of Gly-Gly-His, Gly-His-Lys and their copper complexes on the TNF-α – dependent IL-6 secretion in normal human dermal fibroblasts
5. The influence of inositol hexaphosphate on the expression of genes encoding matrix metalloproteinases 2 and 9 and their tissue inhibitors in human colon cancer cells
6. Expression of matrix metalloproteinase 2 and matrix metalloproteinase 9 in laryngeal squamous cell carcinoma