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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) Adhesion of prostate cancer cells to extracellular matrix proteins. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Cells were added to immobilized collagen, laminin or fibronectin at a density of 0.5 × 106 cells/well for 60 min. Plastic dishes were used to evaluate unspecific binding (background control). One representative of six experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) PC-3 cell migration (left) and invasion (right). Cells treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls were set to 100%. * = significant difference to controls. # = significant difference to single drug treatment.
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fig03: (A) Adhesion of prostate cancer cells to extracellular matrix proteins. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Cells were added to immobilized collagen, laminin or fibronectin at a density of 0.5 × 106 cells/well for 60 min. Plastic dishes were used to evaluate unspecific binding (background control). One representative of six experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) PC-3 cell migration (left) and invasion (right). Cells treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls were set to 100%. * = significant difference to controls. # = significant difference to single drug treatment.

Mentions: Cell adhesion to the extracellular matrix proteins, collagen, fibronectin and laminin, is shown in Figure3A. IFNα exerted no effect on tumour cell adhesion. Whereas everolimus blocked cellular attachment only to laminin, VPA inhibited adhesion to all three matrix proteins. TD further diminished attachment to fibronectin and laminin. Its effect on collagen was similar to that of VPA.


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) Adhesion of prostate cancer cells to extracellular matrix proteins. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Cells were added to immobilized collagen, laminin or fibronectin at a density of 0.5 × 106 cells/well for 60 min. Plastic dishes were used to evaluate unspecific binding (background control). One representative of six experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) PC-3 cell migration (left) and invasion (right). Cells treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls were set to 100%. * = significant difference to controls. # = significant difference to single drug treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig03: (A) Adhesion of prostate cancer cells to extracellular matrix proteins. PC-3 cells were treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Cells were added to immobilized collagen, laminin or fibronectin at a density of 0.5 × 106 cells/well for 60 min. Plastic dishes were used to evaluate unspecific binding (background control). One representative of six experiments is shown. * indicates significant difference to controls, # indicates significant difference to single drug treatment. (B) PC-3 cell migration (left) and invasion (right). Cells treated with 100 U/ml IFNα, 1 nM everolimus or 1 mM VPA, or with all compounds simultaneously (TD). Controls were set to 100%. * = significant difference to controls. # = significant difference to single drug treatment.
Mentions: Cell adhesion to the extracellular matrix proteins, collagen, fibronectin and laminin, is shown in Figure3A. IFNα exerted no effect on tumour cell adhesion. Whereas everolimus blocked cellular attachment only to laminin, VPA inhibited adhesion to all three matrix proteins. TD further diminished attachment to fibronectin and laminin. Its effect on collagen was similar to that of VPA.

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