title: Survival of primary, but not of cancer cells after combined Plk1-HDAC inhibition.
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.
authors: Friedrich-Schiller-University, CMB, Institute for Biochemistry and Biophysics, 07745 Jena, Germany.
authors: Lisa
authors: L
authors: Lange
authors: Leibniz-Institute for Age Research-Fritz Lipmann Institute, JenAge (Jena Centre for Systems Biology of Aging), 07745 Jena, Germany.
authors: Peter
authors: P
authors: Hemmerich
authors: Friedrich-Schiller-University, CMB, Institute for Biochemistry and Biophysics, 07745 Jena, Germany.
authors: Birgit
authors: B
authors: Spänkuch
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D053148:Caspase 3 / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000077337:Vorinostat; D000097869:Polo-Like Kinase 1
chemical_list: D001596:Benzylamines; D053148:Caspase 3; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011065:Poly(ADP-ribose) Polymerases; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D016160:Retinoblastoma Protein; D019098:Telomerase; D000077337:Vorinostat; D000097869:Polo-Like Kinase 1; C493956:CDKN1A protein, human; C549033:SBE13 compound; C509186:TERT protein, human; C505407:CASP3 protein, human
keywords: HDAC; cancer; cell cycle; p21; polo-like kinase 1