Oncotarget

Research Papers:

Survival of primary, but not of cancer cells after combined Plk1-HDAC inhibition

Lisa Lange, Peter Hemmerich and Birgit Spänkuch _

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Oncotarget. 2015; 6:25801-25814. https://doi.org/10.18632/oncotarget.4445

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Abstract

Lisa Lange1, Peter Hemmerich2, Birgit Spänkuch1

1Friedrich-Schiller-University, CMB, Institute for Biochemistry and Biophysics, 07745 Jena, Germany

2Leibniz-Institute for Age Research-Fritz Lipmann Institute, JenAge (Jena Centre for Systems Biology of Aging), 07745 Jena, Germany

Correspondence to:

Birgit Spänkuch, e-mail: [email protected]

Keywords: polo-like kinase 1, HDAC, p21, cell cycle, cancer

Abbreviations: Plk1 - polo-like kinase 1; HDAC - histone deacetylase; HDACi - histone deacetylase inhibitor; SAHA - suberoylanilide hydroxamic acid; pRb - phospho-Rb

Received: February 24, 2015     Accepted: June 16, 2015     Published: June 26, 2015

ABSTRACT

In the current study we examined the combination of SAHA and SBE13 in cancer and non-cancer cells. HeLa cells displayed a synergistically reduced cell proliferation, which was much weaker in hTERT-RPE1 or NIH-3T3 cells. Cell cycle distribution differed in HeLa, hTERT-RPE1 and NIH-3T3 cells. SAHA-treated HeLa cells showed slightly increasing cell numbers in G2/M phase, but after combination with SBE13 strongly elevated cell numbers in G2/M and S phase, accompanied by decreasing G0/G1 percentages. hTERT-RPE1 and NIH-3T3 cells showed strongly enriched cell numbers in G0/G1 phase. Western blot and quantitative real time analyses revealed reduced Plk1 mRNA and protein in all cells. p21 protein was strongly induced in cancer, but not in non-cancer cells, corresponding to a different localization in immunofluorescence studies. Additionally, these revealed an abundantly present pRb protein in HeLa cells after any treatment but almost completely vanished pRb staining in treated hTERT-RPE1 cells. These differences could be approved in Western blots against Parp and Caspase 3, which were activated in HeLa, but not in hTERT-RPE1 cells. Thus, we observed for the first time a differential effect of cancer versus non-cancer cells after treatment with SAHA and SBE13, which might be due to the dual role of p21.


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