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Molecular and Cellular Biochemistry

, Volume 407, Issue 1–2, pp 97–109

First Online: 24 May 2015Received: 16 January 2015Accepted: 16 May 2015DOI: 10.1007-s11010-015-2458-3

Cite this article as: Moskot, M., Jakóbkiewicz-Banecka, J., Smolińska, E. et al. Mol Cell Biochem 2015 407: 97. doi:10.1007-s11010-015-2458-3

Abstract

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.

KeywordsFlavonoids Cell cycle regulation DNA replication process Gene expression profiling Cell growth An erratum to this article is available at http:-dx.doi.org-10.1007-s11010-016-2852-5.

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