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

Bryan G. Allen, Sudershan K. Bhatia, John M. Buatti, Kristin E. Brandt, Kaleigh E. Lindholm, Anna M. Button, Luke I. Szweda, Brian J. Smith, Douglas R. Spitz, Melissa A. Fath

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Purpose: 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 radiochemo- therapy responses in lung cancer xenografts by enhancing oxidative stress. Experimental Design: 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 γH2AX as indices of proliferation and DNA damage, respectively. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)3905-3913
Number of pages9
JournalClinical Cancer Research
Volume19
Issue number14
DOIs
StatePublished - Jul 15 2013

Fingerprint

Ketogenic Diet
Radio
Heterografts
Lung Neoplasms
Oxidative Stress
Radiation
Carboplatin
Proliferating Cell Nuclear Antigen
Neoplasms
Therapeutics
Proteins
Fats
Carbohydrates
Radiation Dosage
Chemoradiotherapy
Glycolysis
Growth
Tumor Burden
Energy Metabolism
Lipid Peroxidation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Allen, B. G., Bhatia, S. K., Buatti, J. M., Brandt, K. E., Lindholm, K. E., Button, A. M., ... Fath, M. A. (2013). Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. Clinical Cancer Research, 19(14), 3905-3913. https://doi.org/10.1158/1078-0432.CCR-12-0287

Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. / Allen, Bryan G.; Bhatia, Sudershan K.; Buatti, John M.; Brandt, Kristin E.; Lindholm, Kaleigh E.; Button, Anna M.; Szweda, Luke I.; Smith, Brian J.; Spitz, Douglas R.; Fath, Melissa A.

In: Clinical Cancer Research, Vol. 19, No. 14, 15.07.2013, p. 3905-3913.

Research output: Contribution to journalArticle

Allen, BG, Bhatia, SK, Buatti, JM, Brandt, KE, Lindholm, KE, Button, AM, Szweda, LI, Smith, BJ, Spitz, DR & Fath, MA 2013, 'Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts', Clinical Cancer Research, vol. 19, no. 14, pp. 3905-3913. https://doi.org/10.1158/1078-0432.CCR-12-0287
Allen, Bryan G. ; Bhatia, Sudershan K. ; Buatti, John M. ; Brandt, Kristin E. ; Lindholm, Kaleigh E. ; Button, Anna M. ; Szweda, Luke I. ; Smith, Brian J. ; Spitz, Douglas R. ; Fath, Melissa A. / Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 14. pp. 3905-3913.
@article{ceac8add9da2477bbb2dec841f8f108b,
title = "Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts",
abstract = "Purpose: 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 radiochemo- therapy responses in lung cancer xenografts by enhancing oxidative stress. Experimental Design: 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 γH2AX as indices of proliferation and DNA damage, respectively. Results: 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. Conclusions: 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.",
author = "Allen, {Bryan G.} and Bhatia, {Sudershan K.} and Buatti, {John M.} and Brandt, {Kristin E.} and Lindholm, {Kaleigh E.} and Button, {Anna M.} and Szweda, {Luke I.} and Smith, {Brian J.} and Spitz, {Douglas R.} and Fath, {Melissa A.}",
year = "2013",
month = "7",
day = "15",
doi = "10.1158/1078-0432.CCR-12-0287",
language = "English (US)",
volume = "19",
pages = "3905--3913",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "14",

}

TY - JOUR

T1 - Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts

AU - Allen, Bryan G.

AU - Bhatia, Sudershan K.

AU - Buatti, John M.

AU - Brandt, Kristin E.

AU - Lindholm, Kaleigh E.

AU - Button, Anna M.

AU - Szweda, Luke I.

AU - Smith, Brian J.

AU - Spitz, Douglas R.

AU - Fath, Melissa A.

PY - 2013/7/15

Y1 - 2013/7/15

N2 - Purpose: 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 radiochemo- therapy responses in lung cancer xenografts by enhancing oxidative stress. Experimental Design: 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 γH2AX as indices of proliferation and DNA damage, respectively. Results: 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. Conclusions: 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.

AB - Purpose: 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 radiochemo- therapy responses in lung cancer xenografts by enhancing oxidative stress. Experimental Design: 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 γH2AX as indices of proliferation and DNA damage, respectively. Results: 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. Conclusions: 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.

UR - http://www.scopus.com/inward/record.url?scp=84881135707&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881135707&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-12-0287

DO - 10.1158/1078-0432.CCR-12-0287

M3 - Article

C2 - 23743570

AN - SCOPUS:84881135707

VL - 19

SP - 3905

EP - 3913

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 14

ER -