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Intensified antineoplastic effect by combining an HDAC-inhibitor, an mTOR-inhibitor and low dosed interferon alpha in prostate cancer cells.

Tsaur I, Hudak L, Makarević J, Juengel E, Mani J, Borgmann H, Gust KM, Schilling D, Bartsch G, Nelson K, Haferkamp A, Blaheta RA - J. Cell. Mol. Med. (2015)

Bottom Line: The triple application of VPA, everolimus and low dosed IFNα blocked tumour cell growth and dissemination significantly better than any agent alone.Antitumour effects were associated with pronounced alteration in the cell cycle machinery, intracellular signalling and integrin expression profile.Combining VPA, everolimus and low dosed IFNα might be a promising option to counteract resistance development and improve outcome in PCa patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.

No MeSH data available.


Related in: MedlinePlus

(A) Cell cycle analysis of PC-3 cells. Tumour cells were treated either with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Cell cycle analysis was carried out after 24 hrs. The cell population at each checkpoint is expressed as percentage of total analysed cells. One representative experiment of three is shown. (B) Western blot of cell cycle proteins. PC-3 cells were treated either with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. β-actin served as the internal control. The figure shows one representative from three separate experiments.
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fig02: (A) Cell cycle analysis of PC-3 cells. Tumour cells were treated either with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Cell cycle analysis was carried out after 24 hrs. The cell population at each checkpoint is expressed as percentage of total analysed cells. One representative experiment of three is shown. (B) Western blot of cell cycle proteins. PC-3 cells were treated either with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. β-actin served as the internal control. The figure shows one representative from three separate experiments.

Mentions: Valproic acid decreased the G2/M- and S-phase and distinctly augmented the G0/G1-phase cells, compared to control (Fig.2A). Everolimus also reduced the G2/M-phase, but increased the number of S-phase cells. IFNα enhanced the S-phase and reduced the G2/M- and G0/G1-phase. Application of TD caused more cells to remain in the G0/G1-phase and fewer in the S- phases compared to any single drug. The Annexin V-FITC-assay showed no increase in apoptotic events with any of the drugs alone or during the triple application (data not shown).


Intensified antineoplastic effect by combining an HDAC-inhibitor, an mTOR-inhibitor and low dosed interferon alpha in prostate cancer cells.

Tsaur I, Hudak L, Makarević J, Juengel E, Mani J, Borgmann H, Gust KM, Schilling D, Bartsch G, Nelson K, Haferkamp A, Blaheta RA - J. Cell. Mol. Med. (2015)

(A) Cell cycle analysis of PC-3 cells. Tumour cells were treated either with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Cell cycle analysis was carried out after 24 hrs. The cell population at each checkpoint is expressed as percentage of total analysed cells. One representative experiment of three is shown. (B) Western blot of cell cycle proteins. PC-3 cells were treated either with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. β-actin served as the internal control. The figure shows one representative from three separate experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549030&req=5

fig02: (A) Cell cycle analysis of PC-3 cells. Tumour cells were treated either with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Cell cycle analysis was carried out after 24 hrs. The cell population at each checkpoint is expressed as percentage of total analysed cells. One representative experiment of three is shown. (B) Western blot of cell cycle proteins. PC-3 cells were treated either with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. β-actin served as the internal control. The figure shows one representative from three separate experiments.
Mentions: Valproic acid decreased the G2/M- and S-phase and distinctly augmented the G0/G1-phase cells, compared to control (Fig.2A). Everolimus also reduced the G2/M-phase, but increased the number of S-phase cells. IFNα enhanced the S-phase and reduced the G2/M- and G0/G1-phase. Application of TD caused more cells to remain in the G0/G1-phase and fewer in the S- phases compared to any single drug. The Annexin V-FITC-assay showed no increase in apoptotic events with any of the drugs alone or during the triple application (data not shown).

Bottom Line: The triple application of VPA, everolimus and low dosed IFNα blocked tumour cell growth and dissemination significantly better than any agent alone.Antitumour effects were associated with pronounced alteration in the cell cycle machinery, intracellular signalling and integrin expression profile.Combining VPA, everolimus and low dosed IFNα might be a promising option to counteract resistance development and improve outcome in PCa patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany.

No MeSH data available.


Related in: MedlinePlus