Research article Special Issues

Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells

  • Received: 01 November 2017 Accepted: 01 February 2018 Published: 08 February 2018
  • HDAC inhibitors (HDACIs) induce irreversible cell cycle arrest and senescence in mouse embryonic fibroblasts transformed with E1A and c-Ha-Ras oncogenes (E1A+Ras cell line). The aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. It’s known that HDACs regulate the ROS-dependent FoxO factors, which are responsible for cell growth, proliferation, and longevity. The characteristic ROS increase during aging may be responsible for the decreased HDAC activity, which facilitates the senescent-like phenotype. The objective of this study was to investigate the impact of FoxO transcription factors on HDACIs-induced senescence of E1A+Ras oncogenes transformed cells. This study shows the specific time-dependent effect of HDACI sodium butyrate treatment on FoxO proteins in E1A+Ras cells. Indeed, short-term treatment with NaB results in FoxO activation, which takes place through nuclear translocation, and accompanied by accumulation of such ROS scavengers as MnSOD and SOD2. However, prolonged treatment leads to extensive FoxO degradation and increased intracellular levels of ROS. This degradation is connected with NaB-induced activation of Akt kinase. All of these findings establish that one of the possible mechanism involved in NaB-induced senescence of transformed cells is mediated through down-regulation of FoxO transcription factors and ROS accumulation.

    Citation: Alisa Morshneva, Olga Gnedina, Svetlana Svetlikova, Valery Pospelov, Maria Igotti. Time-dependent modulation of FoxO activity by HDAC inhibitor in oncogene-transformed E1A+Ras cells[J]. AIMS Genetics, 2018, 5(1): 41-52. doi: 10.3934/genet.2018.1.41

    Related Papers:

  • HDAC inhibitors (HDACIs) induce irreversible cell cycle arrest and senescence in mouse embryonic fibroblasts transformed with E1A and c-Ha-Ras oncogenes (E1A+Ras cell line). The aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. It’s known that HDACs regulate the ROS-dependent FoxO factors, which are responsible for cell growth, proliferation, and longevity. The characteristic ROS increase during aging may be responsible for the decreased HDAC activity, which facilitates the senescent-like phenotype. The objective of this study was to investigate the impact of FoxO transcription factors on HDACIs-induced senescence of E1A+Ras oncogenes transformed cells. This study shows the specific time-dependent effect of HDACI sodium butyrate treatment on FoxO proteins in E1A+Ras cells. Indeed, short-term treatment with NaB results in FoxO activation, which takes place through nuclear translocation, and accompanied by accumulation of such ROS scavengers as MnSOD and SOD2. However, prolonged treatment leads to extensive FoxO degradation and increased intracellular levels of ROS. This degradation is connected with NaB-induced activation of Akt kinase. All of these findings establish that one of the possible mechanism involved in NaB-induced senescence of transformed cells is mediated through down-regulation of FoxO transcription factors and ROS accumulation.


    加载中
    [1] Greer EL, Brunet A (2005) FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24: 7410–7425. doi: 10.1038/sj.onc.1209086
    [2] Klotz L, Sánchez-ramos C, Prieto-arroyo I, et al. (2015) Redox regulation of FoxO transcription factors. Redox Biol 6: 51–72. doi: 10.1016/j.redox.2015.06.019
    [3] Beharry A, Sandesara P, Roberts B, et al. (2014) HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy. J Cell Sci 127: 1441–1453. doi: 10.1242/jcs.136390
    [4] Wang F, Chan C, Chen K, et al. (2011) Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation. Oncogene 31: 1546–1557.
    [5] Furukawa-Hibi Y, Kobayashi Y, Chen C, et al. (2005) FOXO transcription factors in cell-cycle regulation and the response to oxidative stress. Antioxid Redox Signal 7: 752–760. doi: 10.1089/ars.2005.7.752
    [6] Huang H, Tindall D (2007) Dynamic FoxO transcription factors. J Cell Sci 120: 2479–2487. doi: 10.1242/jcs.001222
    [7] Calnan В, Brunet A (2008) The FoxO code. Oncogene 27: 2276–2288. doi: 10.1038/onc.2008.21
    [8] Su J, Cheng X, Yamaguchi H, et al. (2011) FOXO3a-dependent mechanism of E1A-induced chemosensitization. Cancer Res 71: 6878–6888. doi: 10.1158/0008-5472.CAN-11-0295
    [9] van der Heide L, Smidt M (2005) Regulation of FoxO activity by CBP/p300-mediated acetylation. Trends Biochem Sci 30: 81–86. doi: 10.1016/j.tibs.2004.12.002
    [10] Silva J, Bulman C, McMahon M (2015) BRAFV600E cooperates with PI3'-kinase signaling, independent of AKT, to regulate melanoma cell proliferation. Mol Cancer Res 12: 447–463.
    [11] Huang W, Ren C, Huang G, et al. (2017) Inhibition of store-operated Ca2+ entry counteracts the apoptosis of nasopharyngeal carcinoma cells induced by sodium butyrate. Oncol lett 13: 921–929. doi: 10.3892/ol.2016.5469
    [12] Pant K, Yadav A, Gupta P, et al. (2017) Redox Biology Butyrate induces ROS-mediated apoptosis by modulating miR-22/SIRT-1 pathway in hepatic cancer cells. Redox Biol 12: 340–349. doi: 10.1016/j.redox.2017.03.006
    [13] Seifrtová M, Havelek R, Cahlíková L, et al. (2017) Haemanthamine alters sodium butyrate-induced histone acetylation, p21 WAF1/Cip1 expression, Chk1 and Chk2 activation and leads to increased growth inhibition and death in A2780 ovarian cancer cells. Phytomedicine 35: 1–10. doi: 10.1016/j.phymed.2017.08.019
    [14] Abramova MV, Zatulovskiy EA, Svetlikova SB, et al. (2010) HDAC inhibitor-induced activation of NF-κB prevents apoptotic response of E1A+Ras-transformed cells to proapoptotic stimuli. Int J Biochem Cell Biol 42: 1847–1855. doi: 10.1016/j.biocel.2010.08.001
    [15] Abramova M, Pospelova T, Nikulenkov F, et al. (2006) G1/S Arrest induced by histone deacetylase inhibitor sodium butyrate in E1A+ Ras-transformed cells is mediated through down-regulation of E2F activity and stabilization of beta-Catenin. J Biol Chem 281: 21040–21051. doi: 10.1074/jbc.M511059200
    [16] Pospelova TV, Demidenko ZN, Bukreeva EI, et al. (2009) Pseudo-DNA damage response in senescent cells. Cell Cycle 8: 4112–4118. doi: 10.4161/cc.8.24.10215
    [17] Oh SY, Sohn YW, Park JW, et al. (2007) Selective cell death of oncogenic Akt-transduced brain cancer cells by etoposide through reactive oxygen species mediated damage. Mol Cancer Ther 6: 2178–2187. doi: 10.1158/1535-7163.MCT-07-0111
    [18] Alessi DR, Andjelkovic M, Caudwell B, et al. (1996) Mechanism of activation of protein kinase B by insulin and IGF-1. The EMBO J 15: 6541–6551.
    [19] Lu Q, Zhai Y, Cheng Q, et al. (2013) The Akt–FoxO3a–manganese superoxide dismutase pathway is involved in the regulation of oxidative stress in diabetic nephropathy. Exp Physiol 4: 934–945.
    [20] Fallarino F, Bianchi R, Orabona C, et al. (2004) CTLA-4–Ig Activates Forkhead Transcription Factors and Protects Dendritic Cells from Oxidative Stress in Nonobese Diabetic Mice. J Exp Med 200: 1051–1062. doi: 10.1084/jem.20040942
    [21] Yang L, Li C, Wan Y, et al. (2014) Antioxidative fullerol promotes osteogenesis of Antioxidative fullerol promotes osteogenesis of human adipose-derived stem cells. Int J Nanomed 9: 4023–4031.
    [22] Morgan MJ, Liu Z (2010) Crosstalk of reactive oxygen species and NF- κ B signaling. Cell Res 21: 103–115.
    [23] Nogueira V, Park Y, Chen C, et al. (2011) Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis. Cancer 14: 458–470.
    [24] Sealy L, Chalkley R (1978) The effect of sodium butyrate on histone modification. Cell 14: 115–121. doi: 10.1016/0092-8674(78)90306-9
    [25] Zhao Y, Hu X, Liu Y, et al. (2017) ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway. Mol Cancer 16: 79. doi: 10.1186/s12943-017-0648-1
    [26] Plas DR, Thompson CB (2005) Akt-dependent transformation: There is more to growth than just surviving. Oncogene 24: 7435–7442. doi: 10.1038/sj.onc.1209097
    [27] Romanov V, Abramova M, Svetlikova S, et al. (2010) p21Waf1 is required for cellular senescence but not for cell cycle arrest induced by the HDAC inhibitor sodium butyrate. Cell Cycle 9: 3945–3955. doi: 10.4161/cc.9.19.13160
  • Reader Comments
  • © 2018 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(3778) PDF downloads(969) Cited by(6)

Article outline

Figures and Tables

Figures(6)

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog