RRC ID |
82495
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Author |
Zhang N, Liu C, Jin L, Zhang R, Wang T, Wang Q, Chen J, Yang F, Siebert HC, Zheng X.
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Title |
Ketogenic Diet Elicits Antitumor Properties through Inducing Oxidative Stress, Inhibiting MMP-9 Expression, and Rebalancing M1/M2 Tumor-Associated Macrophage Phenotype in a Mouse Model of Colon Cancer.
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Journal |
J Agric Food Chem
|
Abstract |
Many advanced cancers are characterized by metabolic disorders. A dietary therapeutic strategy was proposed to inhibit tumor growth through administration of low-carbohydrate, average-protein, and high-fat diet, which is also known as ketogenic diet (KD). In vivo antitumor efficacy of KD on transplanted CT26+ tumor cells in BALB/c mice was investigated. The results showed that the KD group had significantly higher blood β-hydroxybutyrate and lower blood glucose levels when compared with the normal diet group. Meanwhile, KD increased intratumor oxidative stress, and TUNEL staining showed KD-induced apoptosis against tumor cells. Interestingly, the distribution of CD16/32+ and iNOS+ M1 tumor-associated macrophages (TAMs) increased in the KD-treated group, with concomitantly less arginase-1+ M2 TAMs. Moreover, KD treatment downregulated the protein expression of matrix metalloproteinase-9 in CT26+ tumor-bearing mice. Western blot analysis demonstrated that the expression levels of HDAC3/PKM2/NF-κB 65/p-Stat3 proteins were reduced in the KD-treated group. Taken together, our results indicated that KD can prevent the progression of colon tumor via inducing intratumor oxidative stress, inhibiting the expression of the MMP-9, and enhancing M2 to M1 TAM polarization. A novel potential mechanism was identified that KD can prevent the progression of colon cancer by regulating the expression of HDAC3/PKM2/NF-κB65/p-Stat3 axis.
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Volume |
68(40)
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Pages |
11182-11196
|
Published |
2020-10-7
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DOI |
10.1021/acs.jafc.0c04041
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PMID |
32786841
|
MeSH |
Animals
Cell Line, Tumor
Colonic Neoplasms / diet therapy*
Colonic Neoplasms / genetics
Colonic Neoplasms / immunology*
Diet, Ketogenic*
Disease Models, Animal
Humans
Male
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / immunology*
Mice
Mice, Inbred BALB C
NF-kappa B / genetics
NF-kappa B / immunology
Oxidative Stress*
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / immunology
Tumor-Associated Macrophages / immunology*
|
Resource |
Human and Animal Cells |
Colon-26(RCB2657) |