Alina Sesarman1, Lucia Tefas2, Bianca Sylvester2, Emilia Licarete3, Valentin Rauca3, Lavinia Luput3, Laura Patras3, Manuela Banciu4, Alina Porfire2. 1. Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, Cluj-Napoca, Romania; Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania. 2. Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania. 3. Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, Cluj-Napoca, Romania. 4. Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, Cluj-Napoca, Romania. Electronic address: manuela.banciu@ubbcluj.ro.
Abstract
BACKGROUND: Emerging 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). METHODS: The 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. RESULTS: Our 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. CONCLUSION: LCL-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.
BACKGROUND: Emerging 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 murinecolon carcinoma cells (C26). METHODS: The 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. RESULTS: Our 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. CONCLUSION:LCL-CURC-DOX demonstrated enhanced cytotoxicity on C26 murinecolon 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.
Authors: Adriana E Bulboacă; Sorana D Bolboacă; Ioana C Stănescu; Carmen A Sfrângeu; Alina Porfire; Lucia Tefas; Angelo C Bulboacă Journal: Int J Nanomedicine Date: 2018-05-25