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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 growth analysis of PC-3, DU-145 and LNCaP cells. Tumour cells were treated with either 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Cells were counted after 24, 48 and 72 hrs. One representative experiment of six is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) Adhesion of prostate cancer cells to HUVEC. PC-3, DU-145 and LNCaP cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Tumour cells were added at a density of 0.5 × 106 cells/well to HUVEC monolayers for 1, 2 or 4 hrs. Non-adherent tumour cells were washed off and the remaining cells fixed and counted in five different fields (5 × 0.25 mm2). Mean values were calculated from five counts. One representative of six experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment.
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fig01: (A) Cell growth analysis of PC-3, DU-145 and LNCaP cells. Tumour cells were treated with either 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Cells were counted after 24, 48 and 72 hrs. One representative experiment of six is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) Adhesion of prostate cancer cells to HUVEC. PC-3, DU-145 and LNCaP cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Tumour cells were added at a density of 0.5 × 106 cells/well to HUVEC monolayers for 1, 2 or 4 hrs. Non-adherent tumour cells were washed off and the remaining cells fixed and counted in five different fields (5 × 0.25 mm2). Mean values were calculated from five counts. One representative of six experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment.

Mentions: Valproic acid and everolimus significantly inhibited the growth of PC-3, DU-145 and LNCaP cells, whereas IFNα exerted no significant decrease in cell growth in any cell line (Fig.1A). TD application resulted in nearly complete inhibition of tumour cell growth in all three cell lines.


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 growth analysis of PC-3, DU-145 and LNCaP cells. Tumour cells were treated with either 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Cells were counted after 24, 48 and 72 hrs. One representative experiment of six is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) Adhesion of prostate cancer cells to HUVEC. PC-3, DU-145 and LNCaP cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Tumour cells were added at a density of 0.5 × 106 cells/well to HUVEC monolayers for 1, 2 or 4 hrs. Non-adherent tumour cells were washed off and the remaining cells fixed and counted in five different fields (5 × 0.25 mm2). Mean values were calculated from five counts. One representative of six experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4549030&req=5

fig01: (A) Cell growth analysis of PC-3, DU-145 and LNCaP cells. Tumour cells were treated with either 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Cells were counted after 24, 48 and 72 hrs. One representative experiment of six is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) Adhesion of prostate cancer cells to HUVEC. PC-3, DU-145 and LNCaP cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls remained untreated. Tumour cells were added at a density of 0.5 × 106 cells/well to HUVEC monolayers for 1, 2 or 4 hrs. Non-adherent tumour cells were washed off and the remaining cells fixed and counted in five different fields (5 × 0.25 mm2). Mean values were calculated from five counts. One representative of six experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment.
Mentions: Valproic acid and everolimus significantly inhibited the growth of PC-3, DU-145 and LNCaP cells, whereas IFNα exerted no significant decrease in cell growth in any cell line (Fig.1A). TD application resulted in nearly complete inhibition of tumour cell growth in all three cell lines.

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