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Anti-angiogenic and anti-inflammatory effects of long-circulating liposomes co-encapsulating curcumin and doxorubicin on C26 murine colon cancer cells |
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| Authors: | Alina Sesarman Lucia Tefas Bianca Sylvester Emilia Licarete Valentin Rauca Lavinia Luput Laura Patras Manuela Banciu Alina Porfire |
| Institution: | 1. Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania;2. Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, Cluj-Napoca, Romania;3. Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania |
| Abstract: | BackgroundEmerging treatment options for colon cancer are needed to overcome the limitations regarding the side effects of current chemotherapeutics and drug resistance. The goal of this study was to assess the antitumor actions of PEGylated long-circulating liposomes (LCL) co-delivering curcumin (CURC) and doxorubicin (DOX) on murine colon carcinoma cells (C26).MethodsThe cytotoxicity of CURC and DOX, administered alone or in combination, either in free or LCL form, was evaluated with regard to antiproliferative effects on C26 cells and to protumor processes that might be affected.ResultsOur results indicated that PEGylated LCL-CURC-DOX exerted strong antiproliferative effects on C26 cells, slightly exceeding those induced by free CURC-DOX, but higher than either agent administered alone in their free form. These effects of LCL-CURC-DOX were due to the inhibition of the production of angiogenic/inflammatory proteins in a NF-κB-dependent manner, but were independent of ROS production or AP-1 c-Jun activation. Notable, the anti-angiogenic actions of LCL-CURC-DOX appeared to be much stronger than those induced by the co-administration of CURC and DOX in their free form, on C26 colon cancer cells.ConclusionLCL-CURC-DOX demonstrated enhanced cytotoxicity on C26 murine colon cancer cells by inhibiting the production of the majority of factors involved in tumor-associated angiogenesis and inflammation and is now being evaluated in vivo regarding its efficacy towards tumor growth in colon cancer. |
| Keywords: | AP-1 activator protein 1 AP-1 c-Jun c-Jun subunit of activator protein 1 bFGF basic fibroblast growth factor BrdU bromodeoxyuridine CURC curcumin DOX doxorubicin DPPC FasL Fas ligand FCS fetal calf serum G-CSF granulocyte-colony stimulating factor HPLC high-performance liquid chromatography IFN-γ interferon γ IGF insulin-like growth factor IGF-II insulin-like growth factor II IL-1α interleukin-1α IL-1ß interleukin-1ß IL–4 interleukin-4 IL–6 interleukin-6 IL–8 interleukin-8 IL–9 interleukin-9 IL–10 interleukin-10 IL–12 interleukin-12 IL-12p40 interleukin-12 subunit p40 IL-12p70 interleukin-12 subunit p70 IL–13 interleukin-13 LCL long-circulating liposomes M-CSF macrophage-colony stimulating factor MCP–1 monocyte chemoattractant protein-1 MDA malondialdehyde NC nitrocellulose NF-κB nuclear factor κB NF-κB p65 p65 subunit of nuclear factor κB pAP-1 c-Jun phosphorylated c-Jun subunit of activator protein 1 PBS phosphate buffered saline PEG polyethylene glycol DSPE pNF-κB p65 phosphorylated p65 subunit of NF-κB PF–4 platelet factor 4 ROS reactive oxygen species SD standard deviation TAC total antioxidant capacity TBS-T tris-buffered saline containing 0 1% Tween-20 TIMP–1 tissue inhibitor of metalloproteinases 1 TIMP–2 tissue inhibitor of metalloproteinases 2 TNF-α tumor necrosis factor α TPO thrombopoietin VEGF vascular endothelial growth factor Doxorubicin Curcumin Liposomes Cytotoxicity Colon cancer |
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