: Oncogenic-driven lipogenic metabolism is a common hallmark of colorectal cancer (CRC) progression. Therefore, there is an urgent need to develop novel therapeutic strategies for metabolic reprogramming. Herein, the metabolic profiles in the plasma between CRC patients and paired healthy controls were compared using metabolomics assays. Matairesinol downregulation was evident in CRC patients, and matairesinol supplementation significantly represses CRC tumorigenesis in azoxymethane/dextran sulfate sodium (AOM/DSS) colitis-associated CRC mice. Matairesinol rewired lipid metabolism to improve the therapeutic efficacy in CRC by inducing mitochondrial damage and oxidative damage and blunting ATP production. Finally, matairesinol-loaded liposomes significantly promoted the enhanced antitumor activity of 5-Fu/leucovorin combined with oxaliplatin (FOLFOX) in CDX and PDX mouse models by restoring chemosensitivity to the FOLFOX regimen. Collectively our findings highlight matairesinol-mediated lipid metabolism reprogramming as a novel druggable strategy to restore CRC chemosensitivity, and this nanoenabled approach for matairesinol will improve the chemotherapeutic efficacy with good biosafety.

Matairesinol nanoparticles restore chemosensitivity and suppress colorectal cancer progression in preclinical models: role of lipid metabolism reprogramming / Wu, Shenshen; Wang, Jiajia; Fu, Zan; Familiari, Giuseppe; Relucenti, Michela; Aschner, Michael; Li, Xiaobo; Chen, Hanqing; Chen, Rui. - In: NANO LETTERS. - ISSN 1530-6992. - 23:5(2023), pp. 1970-1980. [10.1021/acs.nanolett.3c00035]

Matairesinol nanoparticles restore chemosensitivity and suppress colorectal cancer progression in preclinical models: role of lipid metabolism reprogramming

Familiari, Giuseppe;Relucenti, Michela;
2023

Abstract

: Oncogenic-driven lipogenic metabolism is a common hallmark of colorectal cancer (CRC) progression. Therefore, there is an urgent need to develop novel therapeutic strategies for metabolic reprogramming. Herein, the metabolic profiles in the plasma between CRC patients and paired healthy controls were compared using metabolomics assays. Matairesinol downregulation was evident in CRC patients, and matairesinol supplementation significantly represses CRC tumorigenesis in azoxymethane/dextran sulfate sodium (AOM/DSS) colitis-associated CRC mice. Matairesinol rewired lipid metabolism to improve the therapeutic efficacy in CRC by inducing mitochondrial damage and oxidative damage and blunting ATP production. Finally, matairesinol-loaded liposomes significantly promoted the enhanced antitumor activity of 5-Fu/leucovorin combined with oxaliplatin (FOLFOX) in CDX and PDX mouse models by restoring chemosensitivity to the FOLFOX regimen. Collectively our findings highlight matairesinol-mediated lipid metabolism reprogramming as a novel druggable strategy to restore CRC chemosensitivity, and this nanoenabled approach for matairesinol will improve the chemotherapeutic efficacy with good biosafety.
2023
colorectal cancer; lipid droplet; liposome nanoparticles; metabolomics; triglyceride metabolism
01 Pubblicazione su rivista::01a Articolo in rivista
Matairesinol nanoparticles restore chemosensitivity and suppress colorectal cancer progression in preclinical models: role of lipid metabolism reprogramming / Wu, Shenshen; Wang, Jiajia; Fu, Zan; Familiari, Giuseppe; Relucenti, Michela; Aschner, Michael; Li, Xiaobo; Chen, Hanqing; Chen, Rui. - In: NANO LETTERS. - ISSN 1530-6992. - 23:5(2023), pp. 1970-1980. [10.1021/acs.nanolett.3c00035]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1673766
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