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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) Integrin expression on cell surface. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Mean fluorescence units are given in percentage difference to the controls. One of three independent experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) Western blot analysis of integrin protein expression. 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. (C) Integrin gene expression. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. One representative from three separate experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment (i.e. to VPA, IFNα or everolimus).
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fig04: (A) Integrin expression on cell surface. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Mean fluorescence units are given in percentage difference to the controls. One of three independent experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) Western blot analysis of integrin protein expression. 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. (C) Integrin gene expression. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. One representative from three separate experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment (i.e. to VPA, IFNα or everolimus).

Mentions: Interferon alpha exerted no effect on integrin surface expression, whereas VPA enhanced the expression of α1, α3 and β1 and reduced the level of α5, α6 and β4 (Fig.4A). Integrin α4 expression was not detected on the surface of untreated cells (data not shown). Everolimus increased the expression of α2 and β3 and reduced the level of α5. Compared to IFNα, VPA or everolimus alone, when exposed to TD cancer cells demonstrated augmented expression of α2, α3, β1 and β3.


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) Integrin expression on cell surface. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Mean fluorescence units are given in percentage difference to the controls. One of three independent experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) Western blot analysis of integrin protein expression. 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. (C) Integrin gene expression. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. One representative from three separate experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment (i.e. to VPA, IFNα or everolimus).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig04: (A) Integrin expression on cell surface. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Mean fluorescence units are given in percentage difference to the controls. One of three independent experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) Western blot analysis of integrin protein expression. 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. (C) Integrin gene expression. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. One representative from three separate experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment (i.e. to VPA, IFNα or everolimus).
Mentions: Interferon alpha exerted no effect on integrin surface expression, whereas VPA enhanced the expression of α1, α3 and β1 and reduced the level of α5, α6 and β4 (Fig.4A). Integrin α4 expression was not detected on the surface of untreated cells (data not shown). Everolimus increased the expression of α2 and β3 and reduced the level of α5. Compared to IFNα, VPA or everolimus alone, when exposed to TD cancer cells demonstrated augmented expression of α2, α3, β1 and β3.

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