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.
Ning ZhangChunhong LiuLi JinRuiyan ZhangTing WangQingpeng WangJingchao ChenFang YangHans-Christian SiebertXuexing ZhengPublished in: Journal of agricultural and food chemistry (2020)
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.
Keyphrases
- oxidative stress
- induced apoptosis
- signaling pathway
- poor prognosis
- high fat diet
- blood glucose
- physical activity
- endoplasmic reticulum stress
- adipose tissue
- dna damage
- binding protein
- weight loss
- ischemia reperfusion injury
- mouse model
- computed tomography
- diabetic rats
- magnetic resonance imaging
- long non coding rna
- blood pressure
- young adults
- insulin resistance
- magnetic resonance
- pi k akt
- high fat diet induced
- south africa
- image quality
- skeletal muscle
- contrast enhanced
- atomic force microscopy
- heat stress
- risk assessment
- heat shock
- human health