caa a22 4500 606235493 CHVBK 20210128101242.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s11010-015-2458-3 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2458-3 Effects of flavonoids on expression of genes involved in cell cycle regulation and DNA replication in human fibroblasts [Elektronische Daten] [Marta Moskot, Joanna Jakóbkiewicz-Banecka, Elwira Smolińska, Ewa Piotrowska, Grzegorz Węgrzyn, Magdalena Gabig-Cimińska] Flavonoids have been studied as potential agents in medicine for many years. Among them, genistein was found to be active in various biological systems, mainly in prevention of cancer. Our recent work supported the idea that genistein also impacts multiple cellular processes in healthy fibroblasts; however, its effects on cell cycle-related pathways remained to be elucidated. Thus, in this work, high throughput screening with microarrays coupled to real-time quantitative Reverse Transcription PCR analyses was employed to study the changes in expression of key genes associated with cell cycle regulation and/or DNA replication in response to genistein, kaempferol, daidzein, and mixtures of genistein and either kaempferol or daidzein. Among them, genistein was found as the most significantly modulating, in a time- and dose-dependent manner, compound of activity of studied genes, whose products are involved in different phases of the cell cycle and/or in regulatory processes important for DNA replication and cell growth. It considerably reduced the efficiency of expression of genes coding for MCM2-7 and MCM10 helicases, as well as some other proteins involved in the S phase control. In addition, genistein caused cell cycle arrest in the G2/M phase, which was accompanied by activation of CDKN1A, CDKN1C, CDKN2A, CDKN2B, CDKN2C, and GADD45A genes, as well as down-regulation of several mRNAs specific for this stage, demonstrated by transcriptomic assessments. We believe that studies described in this paper will be helpful in elucidating molecular mechanisms of action of genistein as modulator of cell cycle and inhibitor of DNA replication in humans. The Author(s), 2015 Flavonoids nationallicence Cell cycle regulation nationallicence DNA replication process nationallicence Gene expression profiling nationallicence Cell growth nationallicence Moskot Marta Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308, Gdańsk, Poland aut Jakóbkiewicz-Banecka Joanna Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland aut Smolińska Elwira Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland aut Piotrowska Ewa Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland aut Węgrzyn Grzegorz Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland aut Gabig-Cimińska Magdalena Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308, Gdańsk, Poland aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 97-109 0300-8177 407:1-2<97 2015 407 11010 https://doi.org/10.1007/s11010-015-2458-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2458-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Moskot Marta Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308, Gdańsk, Poland aut NATIONALLICENCE 700 1- Jakóbkiewicz-Banecka Joanna Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland aut NATIONALLICENCE 700 1- Smolińska Elwira Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland aut NATIONALLICENCE 700 1- Piotrowska Ewa Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland aut NATIONALLICENCE 700 1- Węgrzyn Grzegorz Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland aut NATIONALLICENCE 700 1- Gabig-Cimińska Magdalena Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308, Gdańsk, Poland aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 407/1-2(2015-09-01), 97-109 0300-8177 407:1-2<97 2015 407 11010