Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines
| Autor: | Yves M. Dupertuis, Claude Pichard, Emmanuelle Angibaud, Florence Delie, Eric Allémann, Nathalie Boulens, Anna-Sophia Briod, Alexandre Viglione |
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| Rok vydání: | 2021 |
| Předmět: |
liposomes
Antimetabolites Antineoplastic Pharmaceutical Science colorectal cancer Apoptosis Aquatic Science chemotherapy 03 medical and health sciences 0302 clinical medicine In vivo Cell Line Tumor Fatty Acids Omega-3 Drug Discovery Chemotherapy Humans 5-fluorouracil Ecology Evolution Behavior and Systematics 030304 developmental biology chemistry.chemical_classification ddc:615 0303 health sciences Liposome Ecology Chemistry General Medicine Cell cycle Colorectal cancer Eicosapentaenoic acid Molecular biology Docosahexaenoic acid 030220 oncology & carcinogenesis Liposomes Colonic Neoplasms Cancer cell Polyunsaturated fatty acids Fluorouracil Colorectal Neoplasms Agronomy and Crop Science Research Article polyunsaturated fatty acids Polyunsaturated fatty acid |
| Zdroj: | AAPS PharmSciTech AAPS PharmSciTech, Vol. 22, No 1 (2021) |
| ISSN: | 1530-9932 |
| DOI: | 10.1208/s12249-020-01897-5 |
| Popis: | It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) could act synergistically with 5-fluorouracil (5-FU) to kill cancer cells. To facilitate their simultaneous transport in the bloodstream, we synthesized, for the first time, liposomes (LIPUFU) containing 5-FU in the aqueous core and docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) at a ratio of 1:2 in the lipid bilayer. LIPUFU werestable with uniform size of 154 ± 4 nm, PDI of 0.19 ± 0.03 and zeta potential of -41 ± 2 mV. They contained 557 ± 210 μmol/l DHA, 1467 ± 362 μmol/l EPA, and 9.8 ± 1.1 μmol/l 5-FU. Control liposomes without (LIP) or with only 5-FU (LIFU) or n-3 PUFAs (LIPU) were produced in a similar way. The effects of these different liposomal formulations on the cell cycle, growth, and apoptosis were evaluated in two human colorectal cancer (CRC) cell lines differing in sensitivity to 5-FU, using fluorescence-activated cell sorting analyses. LIPUFU were more cytotoxic than LIP, LIFU, and LIPU in both LS174T (p53+/+, bax−/−) and HT-29 (p53−/0, bax+/+) cell lines. Similar to LIFU, LIPUFU increased the percentage of cells in S phase, apoptosis, and/or necrosis. The cytotoxic potential of LIPUFU was confirmed in vivo by tumor growth inhibition in the chicken chorioallantoic membrane model. These results suggest that LIPUFU could be considered to facilitate the simultaneous transport of 5-FU and n-3 PUFAs to the tumor site, in particular in case of CRC liver metastases. |
| Databáze: | OpenAIRE |
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