Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglyceridesReport as inadecuate




Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 8:122

First Online: 30 April 2008Received: 25 October 2007Accepted: 30 April 2008DOI: 10.1186-1471-2407-8-122

Cite this article as: Otto, C., Kaemmerer, U., Illert, B. et al. BMC Cancer 2008 8: 122. doi:10.1186-1471-2407-8-122

Abstract

BackgroundAmong the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides MCT.

MethodsTwenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132-87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet KD group; n = 12 or a standard diet SD group; n = 12 ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm to 700 mm. The two diets were compared based on tumour growth and survival time interval between tumour cell injection and attainment of target tumour volume.

ResultsThe ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme.

ConclusionApplication of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further studies are needed to address the impact of this diet on other tumour-relevant functions such as invasive growth and metastasis.

AbbreviationsATPadenosine triphosphate

β-OHBbeta-hydroxybutyrate

CKcytokeratin

CoAcoenzyme A

DMEMDulbecco-s modified Eagle-s medium

EDTAethylenediamine tetraacetic aicd

FCSfetal calf serum

Glut-1glucose transporter type 1

HandEhaematoxyline-eosine

HUVECHuman Umbilical Vein Endothelial Cell

2-NBDG2-N-7-nitrobenz-2-oxa-1,3-diazol-4-ylamino-2-deoxy-D-glucose

PBSPhosphate-buffered saline

23132-87human gastric adenocarcinoma cell line

PETpositron-emmission tomography

RPMI 1640 mediumRoswell Park Memorial Institute

TKTL1transketolase like enzyme 1.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-8-122 contains supplementary material, which is available to authorized users.

Christoph Otto, Ulrike Kaemmerer contributed equally to this work.

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Author: Christoph Otto - Ulrike Kaemmerer - Bertram Illert - Bettina Muehling - Nadja Pfetzer - Rainer Wittig - Hans Ullrich Voelk

Source: https://link.springer.com/







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