Modelling of DHEA effect on CYP1A2 expression in LNCaP and MCF-7 cell lines

Ale Belic, Damjana Rozman, Manna Temesvari, Katalin Toth, K. Monostory, Radim Vrzal, Zdenek Dvorak

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

CYP1A2 enzyme is involved in several metabolic processes that may produce substances with carcinogenic or mutagenic activity. Most commonly it metabolizes the charcoaled food components, polycyclic aromatic hydrocarbons (PAHs) or heterocyclic aromatic amines (HAAs) into mutagenic and cytotoxic substances. Dehydroepiandrosterone (DHEA) is formed endogenously from cholesterol and is a precursor of sex hormones. At pharmacological dosage as food supplement DHEA has several known chemo-protective functions. This study is dedicated to modelling of DHEA action in CYP1A2 expression. Based on the experimental data, a hypothesis was formed that DHEA interacts with CYP1A2 mRNA through androgene receptor (AR). To provide evidence for the hypothesis, dedicated experiments in LNCaP and MCF-7 cell lines were performed. First, the cells were exposed to 3-methylcholantrene (MC) as strong CYP1A2 inducer, MC and DHEA, and MC, DHEA and bicalutamide (BC) a known antagonist of AR in three separate experiments. Next, the physiology based model was constructed and validated on the experimental data. The model suggested that AR can play a role in post-transcriptional phase of CYP1A2 expression regulation. Follow-up experiments with actinomycin D, a strong transcription inhibitor were performed and the results confirmed that DHEA is affecting post-transcriptional phase of CYP1A2 expression and that AR is most likely involved in the mechanism.

Original languageEnglish
Title of host publicationProceedings - 8th EUROSIM Congress on Modelling and Simulation, EUROSIM 2013
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages30-35
Number of pages6
ISBN (Print)9780769550732
DOIs
Publication statusPublished - Jan 8 2015
Event8th EUROSIM Congress on Modelling and Simulation, EUROSIM 2013 - Cardiff, Wales, United Kingdom
Duration: Sep 10 2013Sep 13 2013

Other

Other8th EUROSIM Congress on Modelling and Simulation, EUROSIM 2013
CountryUnited Kingdom
CityCardiff, Wales
Period9/10/139/13/13

Fingerprint

Receptor
Cells
Line
Cell
Modeling
Experiments
Cholesterol
Hormones
Physiology
Experimental Data
Transcription
Polycyclic aromatic hydrocarbons
Experiment
Amines
Hydrocarbons
Enzymes
Precursor
Messenger RNA
Inhibitor
Likely

Keywords

  • breast cancer cell line
  • CYP1A2
  • DHEA
  • Gene expression
  • modelling
  • prostate cancer cell line

ASJC Scopus subject areas

  • Modelling and Simulation
  • Computational Theory and Mathematics
  • Computer Science Applications

Cite this

Belic, A., Rozman, D., Temesvari, M., Toth, K., Monostory, K., Vrzal, R., & Dvorak, Z. (2015). Modelling of DHEA effect on CYP1A2 expression in LNCaP and MCF-7 cell lines. In Proceedings - 8th EUROSIM Congress on Modelling and Simulation, EUROSIM 2013 (pp. 30-35). [7004913] Institute of Electrical and Electronics Engineers Inc.. https://doi.org/10.1109/EUROSIM.2013.114

Modelling of DHEA effect on CYP1A2 expression in LNCaP and MCF-7 cell lines. / Belic, Ale; Rozman, Damjana; Temesvari, Manna; Toth, Katalin; Monostory, K.; Vrzal, Radim; Dvorak, Zdenek.

Proceedings - 8th EUROSIM Congress on Modelling and Simulation, EUROSIM 2013. Institute of Electrical and Electronics Engineers Inc., 2015. p. 30-35 7004913.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Belic, A, Rozman, D, Temesvari, M, Toth, K, Monostory, K, Vrzal, R & Dvorak, Z 2015, Modelling of DHEA effect on CYP1A2 expression in LNCaP and MCF-7 cell lines. in Proceedings - 8th EUROSIM Congress on Modelling and Simulation, EUROSIM 2013., 7004913, Institute of Electrical and Electronics Engineers Inc., pp. 30-35, 8th EUROSIM Congress on Modelling and Simulation, EUROSIM 2013, Cardiff, Wales, United Kingdom, 9/10/13. https://doi.org/10.1109/EUROSIM.2013.114
Belic A, Rozman D, Temesvari M, Toth K, Monostory K, Vrzal R et al. Modelling of DHEA effect on CYP1A2 expression in LNCaP and MCF-7 cell lines. In Proceedings - 8th EUROSIM Congress on Modelling and Simulation, EUROSIM 2013. Institute of Electrical and Electronics Engineers Inc. 2015. p. 30-35. 7004913 https://doi.org/10.1109/EUROSIM.2013.114
Belic, Ale ; Rozman, Damjana ; Temesvari, Manna ; Toth, Katalin ; Monostory, K. ; Vrzal, Radim ; Dvorak, Zdenek. / Modelling of DHEA effect on CYP1A2 expression in LNCaP and MCF-7 cell lines. Proceedings - 8th EUROSIM Congress on Modelling and Simulation, EUROSIM 2013. Institute of Electrical and Electronics Engineers Inc., 2015. pp. 30-35
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