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Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts.

ABSTRACT: Ketogenic diets are high in fat and low in carbohydrates as well as protein which forces cells to rely on lipid oxidation and mitochondrial respiration rather than glycolysis for energy metabolism. Cancer cells (relative to normal cells) are believed to exist in a state of chronic oxidative stress mediated by mitochondrial metabolism. The current study tests the hypothesis that ketogenic diets enhance radio-chemo-therapy responses in lung cancer xenografts by enhancing oxidative stress.Mice bearing NCI-H292 and A549 lung cancer xenografts were fed a ketogenic diet (KetoCal 4:1 fats: proteins+carbohydrates) and treated with either conventionally fractionated (1.8-2 Gy) or hypofractionated (6 Gy) radiation as well as conventionally fractionated radiation combined with carboplatin. Mice weights and tumor size were monitored. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modified proteins as a marker of oxidative stress as well as proliferating cell nuclear antigen (PCNA) and ?H2AX as indices of proliferation and DNA damage, respectively.The ketogenic diets combined with radiation resulted in slower tumor growth in both NCI-H292 and A549 xenografts (P < 0.05), relative to radiation alone. The ketogenic diet also slowed tumor growth when combined with carboplatin and radiation, relative to control. Tumors from animals fed a ketogenic diet in combination with radiation showed increases in oxidative damage mediated by lipid peroxidation as determined by 4HNE-modified proteins as well as decreased proliferation as assessed by decreased immunoreactive PCNA.These results show that a ketogenic diet enhances radio-chemo-therapy responses in lung cancer xenografts by a mechanism that may involve increased oxidative stress.

SUBMITTER: Allen BG

PROVIDER: S-EPMC3954599 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts.

Allen Bryan G BG Bhatia Sudershan K SK Buatti John M JM Brandt Kristin E KE Lindholm Kaleigh E KE Button Anna M AM Szweda Luke I LI Smith Brian J BJ Spitz Douglas R DR Fath Melissa A MA

Clinical cancer research : an official journal of the American Association for Cancer Research 20130606 14

<h4>Purpose</h4>Ketogenic diets are high in fat and low in carbohydrates as well as protein which forces cells to rely on lipid oxidation and mitochondrial respiration rather than glycolysis for energy metabolism. Cancer cells (relative to normal cells) are believed to exist in a state of chronic oxidative stress mediated by mitochondrial metabolism. The current study tests the hypothesis that ketogenic diets enhance radio-chemo-therapy responses in lung cancer xenografts by enhancing oxidative ...[more]

PMID: 23743570

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Project description:BACKGROUND:Radiotherapy treatment of head and neck cancer affects local arteries and increases the risk of stroke. This study aimed at a closer characterization of this damage and its development in time with a longitudinal study set up. METHODS:Male patients treated between 2011 and 2016 for hypopharyngeal carcinoma were identified from the in-house clinical data base. They were included into the study if besides the planning CT at least one additional CT image was available from follow-up (13 patients) or at least two MRI scans (16 patients of which 2 were already included). All patients received radiotherapy, and chemotherapy was administered to 16 patients. The time from the beginning of radiotherapy to the last available image ranged from 2?months to 4.5?years. For six segments of the carotid arteries, the number and volume of atherosclerotic plaques were determined from the CT scans, and the intima media thickness from the MRI scans. Information on comorbid cardiovascular disease, hypertension and diabetes mellitus was retrieved from medical records. RESULTS:Total plaque volume rose from 0.25?cm3 before to 0.33?cm3 after therapy but this was not significant (p?=?0.26). The mean number of plaques increased from 5.7 to 8.1 (p?=?0.002), and the intima media thickened from 1.17?mm to 1.35?mm (p?=?0.002). However, the mean intima media thickness practically did not change in patients with comorbid diabetes mellitus (p-value for homogeneity: 0.03). For patients without diabetes mellitus, dynamics of both plaque number and intima media thickness, was consistent with an increase until about one year after therapy and no further progression thereafter. CONCLUSION:Our study confirmed the thickening of artery walls and the increase in the number of plaques. Results imply that definitive radiation damage to the artery walls can be determined not earlier than about one year after radiotherapy and there is no substantial deterioration thereafter. Reasons for the absence of an observable intima media thickening in patients with diabetes are unclear.

Dataset Information

Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts.

Publications

Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts.

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