Caloric Restriction Prevents Carcinogen-Initiated Liver Tumorigenesis in Mice

Ploeger, Jonathan M.; Manivel, J. Carlos; Boatner, Lauren N.; Mashek, Douglas G.

doi:10.1158/1940-6207.capr-17-0174

Cited by 16 publications

(10 citation statements)

References 53 publications

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“…In a colon cancer model EPA also reduced MMP9 cytokine production via NOTCH1 signaling to exhibit protective effects ( Fazio et al, 2016 ). Alternatively, caloric restriction has been suggested as a mechanism to alter metabolic pathways in NDEA-induced HCC rather than diet leading to altered inflammation, oxidative stress, cell migration, injury and oncogenesis ( Ploeger, Manivel, Boatner, & Mashek, 2017 ). Human plasma and serum found to consist of eicosanoids and SPMs, additional omega-3 or acetylsalicylic acid supplementation also increased plasma SPM levels inducing increased phagocytosis ( Colas, Shinohara, Dalli, Chiang, & Serhan, 2014 ).…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

129

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Inflammation in the tumor microenvironment is a hallmark of cancer and is recognized as a key characteristic of carcinogens. However, the failure of resolution of inflammation in cancer is only recently being understood. Products of arachidonic acid and related fatty acid metabolism called eicosanoids, including prostaglandins, leukotrienes, lipoxins, and epoxyeicosanoids, critically regulate inflammation, as well as its resolution. The resolution of inflammation is now appreciated to be an active biochemical process regulated by endogenous specialized pro-resolving lipid autacoid mediators which combat infections and stimulate tissue repair/regeneration. Environmental and chemical human carcinogens, including aflatoxins, asbestos, nitrosamines, alcohol, and tobacco, induce tumor-promoting inflammation and can disrupt the resolution of inflammation contributing to a devastating global cancer burden. While mechanisms of carcinogenesis have focused on genotoxic activity to induce mutations, nongenotoxic mechanisms such as inflammation and oxidative stress promote genotoxicity, proliferation, and mutations. Moreover, carcinogens initiate oxidative stress to synergize with inflammation and DNA damage to fuel a vicious feedback loop of cell death, tissue damage, and carcinogenesis. In contrast, stimulation of resolution of inflammation may prevent carcinogenesis by clearance of cellular debris via macrophage phagocytosis and inhibition of an eicosanoid/cytokine storm of pro-inflammatory mediators. Controlling the host inflammatory response and its resolution in carcinogen-induced cancers will be critical to reducing carcinogen-induced morbidity and mortality. Here we review the recent evidence that stimulation of resolution of inflammation, including pro-resolution lipid mediators and soluble epoxide hydrolase inhibitors, may be a new chemopreventive approach to prevent carcinogen-induced cancer that should be evaluated in humans.

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Section: Therapeutic Approachesmentioning

confidence: 99%

Carcinogenesis: Failure of resolution of inflammation?

Fishbein

Hammock

Serhan

et al. 2021

Pharmacology & Therapeutics

129

View full text Add to dashboard Cite

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“…Continued studies have shown that as a form of hypurgia, fasting prevents tamoxifen‐induced endometrial hyperplasia and improves the effect of estrogen therapy on hormone receptor‐positive breast cancer 41 . Similarly, CR reduces the incidence of intestinal polyps, 15 liver oncogenesis, 42 and skin tumorigenesis 43 and serves as a potential therapeutic option for colorectal cancer 44 . Fasting also reduces chemotherapy toxicity and prolongs survival time in a mouse model of neuroblastoma 45 .…”

Section: Discussionmentioning

confidence: 99%

Caloric restriction alleviates radiation injuries in a sex‐dependent fashion

Dong

Xiao

et al. 2021

FASEB j.

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Safe and effective regimens are still needed given the risk of radiation toxicity from iatrogenic irradiation. The gut microbiota plays an important role in radiation damage. Diet has emerged as a key determinant of the intestinal microbiome signature and function. In this report, we investigated whether a 30% caloric restriction (CR) diet may ameliorate radiation enteritis and hematopoietic toxicity. Experimental mice were either fed ad libitum (AL) or subjected to CR preconditioning for 10 days and then exposed to total body irradiation (TBI) or total abdominal irradiation (TAI). Gross examinations showed that short-term CR pretreatment restored hematogenic organs and improved the intestinal architecture in both male and female mice. Intriguingly, CR preconditioning mitigated radiation-induced systemic and enteric inflammation in female mice, while gut barrier function improved in irradiated males. 16S rRNA high-throughput sequencing showed that the frequency of pro-inflammatory microbes, including Helicobacter and Desulfovibrionaceae, was reduced in female mice after 10 days of CR preconditioning, while an enrichment of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibaculum, Clostridiales, and Lactobacillus, was observed in males. Using fecal microbiota transplantation (FMT) or antibiotic administration to alter the gut microbiota counteracted the short-term CR-elicited radiation tolerance of both male and female mice, further indicating that the radioprotection of a 30% CR diet depends on altering the gut microbiota. Together, our findings provide new insights into CR in clinical applications and indicate that a short-term CR diet prior to radiation modulates sexspecific gut microbiota configurations, protecting male and female mice against the side effects caused by radiation challenge.

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“…TE also reduced body weight gains caused by HFD, possibly related to green tea’s effects on thermogenesis and fat oxidation (42). In this context, a recent study reported that caloric restriction diet inhibits DEN-induced liver tumorigenesis in mice which may involve multifaceted mechanisms (43). The antioxidant effects of catechins may be due in part to increased activities of catalase, superoxide dismutase and glutathione peroxidase (44).…”

Section: Discussionmentioning

confidence: 99%

Prevention of Lipid Peroxidation–derived Cyclic DNA Adduct and Mutation in High-Fat Diet–induced Hepatocarcinogenesis by Theaphenon E

Coia

Hou

et al. 2018

Cancer Prevention Research

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Obesity is associated with cancer risk and its link with liver cancer is particularly strong. Obesity causes non-alcoholic fatty liver disease (NAFLD) that could progress to hepatocellular carcinoma (HCC). Chronic inflammation likely plays a key role. We carried out a bioassay in the high-fat diet (HFD)-fed C57BL/6J mice to provide insight into the mechanisms of obesity-related HCC by studying γ-OHPdG, a mutagenic DNA adduct derived from lipid peroxidation. In an 80-week bioassay, mice received a low-fat diet (LFD), high-fat diet (HFD), and HFD with 2% Theaphenon E (TE) (HFD+TE). HFD mice developed a 42% incidence of HCC and LFD mice a 16%. Remarkably, TE, a standardized green tea extract formulation, completely blocked HCC in HFD mice with a 0% incidence. γ-OHPdG measured in the hepatic DNA of mice fed HFD and HFD+TE showed its levels increased during the early stages of NAFLD in HFD mice and the increases were significantly suppressed by TE, correlating with the tumor data. Whole-exome sequencing showed an increased mutation load in the liver tumors of HFD mice with G>A and G>T as the predominant mutations, consistent with the report that γ-OHPdG induces G>A and G>T. Furthermore, the mutation loads were significantly reduced in HFD+TE mice, particularly G>T, the most common mutation in human HCC. These results demonstrate in a relevant model of obesity-induced HCC that γ-OHPdG formation during fatty liver disease may be an initiating event for accumulated mutations that leads to HCC and this process can be effectively inhibited by TE. .

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Caloric Restriction Prevents Carcinogen-Initiated Liver Tumorigenesis in Mice

Cited by 16 publications

References 53 publications

Carcinogenesis: Failure of resolution of inflammation?

Carcinogenesis: Failure of resolution of inflammation?

Caloric restriction alleviates radiation injuries in a sex‐dependent fashion

Prevention of Lipid Peroxidation–derived Cyclic DNA Adduct and Mutation in High-Fat Diet–induced Hepatocarcinogenesis by Theaphenon E

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