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.
Keywords:
HDAC; cancer; cell cycle; p21; polo-like kinase 1.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Benzylamines / pharmacology*
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Caspase 3 / pharmacology
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Female
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Fibroblasts / drug effects*
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Fibroblasts / enzymology
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Fibroblasts / pathology
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G2 Phase Cell Cycle Checkpoints / drug effects
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HeLa Cells
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Histone Deacetylase Inhibitors / pharmacology*
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Humans
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Hydroxamic Acids / pharmacology*
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Mice
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NIH 3T3 Cells
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Phosphorylation
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Polo-Like Kinase 1
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Poly(ADP-ribose) Polymerases / metabolism
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Protein Kinase Inhibitors / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Pyridines / pharmacology*
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Retinal Pigment Epithelium / drug effects*
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Retinal Pigment Epithelium / enzymology
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Retinal Pigment Epithelium / pathology
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Retinoblastoma Protein / metabolism
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Signal Transduction / drug effects
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Telomerase / genetics
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Telomerase / metabolism
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Time Factors
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Transfection
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Uterine Cervical Neoplasms / drug therapy*
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Uterine Cervical Neoplasms / enzymology
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Uterine Cervical Neoplasms / genetics
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Uterine Cervical Neoplasms / pathology
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Vorinostat
Substances
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Benzylamines
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins
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Pyridines
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Retinoblastoma Protein
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SBE13 compound
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Vorinostat
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Poly(ADP-ribose) Polymerases
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Protein Serine-Threonine Kinases
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TERT protein, human
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Telomerase
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CASP3 protein, human
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Caspase 3