Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines

Dupertuis, Yves Marc; Boulens, Nathalie; Angibaud, Emmanuelle; Briod, Anna-Sophia; Viglione, Alexandre; Allémann, Eric; Delie Salmon, Florence; Pichard, Claude

doi:10.1208/s12249-020-01897-5

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Title		Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines
Authors		Dupertuis, Yves Marc Boulens, Nathalie Angibaud, Emmanuelle Briod, Anna-Sophia Viglione, Alexandre Allémann, Eric Delie Salmon, Florence Pichard, Claude
Published in		AAPS PharmSciTech. 2021, vol. 22, no. 1
Abstract		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.
Keywords		Colorectal cancer — Chemotherapy — 5-fluorouracil — Polyunsaturated fatty acids — Liposomes
Identifiers		DOI: 10.1208/s12249-020-01897-5 PMID: 33404935
Full text		Article (Published version) (2.6 MB) - Free access Other version: http://link.springer.com/10.1208/s12249-020-01897-5
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine Faculté des sciences / Section des sciences pharmaceutiques
Research groups		Technologie pharmaceutique Nutrition (1038)
Citation (ISO format)		DUPERTUIS, Yves Marc et al. Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines. In: AAPS PharmSciTech, 2021, vol. 22, n° 1. doi: 10.1208/s12249-020-01897-5 https://archive-ouverte.unige.ch/unige:149829