NDLI: Manipulation of tumor metabolism for therapeutic approaches: ovarian cancer-derived cell lines as a model system

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Manipulation of tumor metabolism for therapeutic approaches: ovarian cancer-derived cell lines as a model system

Content Provider	Springer Nature Link
Author	Goetze, Kristina Fabian, Christian G. Siebers, Andrea Binz, Livia Faber, Daniel Indraccolo, Stefano Nardo, Giorgia Sattler, Ulrike G. A. Mueller Klieser, Wolfgang
Copyright Year	2015
Abstract	Malignant transformation of cells is often accompanied by up-regulation of glycolysis-related enzymes and transporters, as well as a distortion of mitochondrial respiration. As a consequence, most malignant tumors utilize high amounts of glucose and produce and accumulate high concentrations of lactate, even in the presence of oxygen. This phenomenon has been termed ‘Warburg Effect’. Here, we aimed at resolving the interrelation between tumor metabolism, reactive oxygen species, double strand DNA breaks and radio-resistance in ovarian cancer-derived cells.As a model system two ovarian cancer-derived cell lines, OC316 and IGROV-1, and its corresponding xenografts were used. First, the metabolic properties of the xenografts were tested to ensure that initial in vitro data might later be transferred to in vivo data. In parallel, three inhibitors of tumor cell metabolism, 2-deoxy-D-glucose, an inhibitor of glycolysis, oxamate, a pyruvate analogue and inhibitor of lactate dehydrogenase, and rotenone, a specific inhibitor of mitochondrial electron complex I, were tested for their effect on the metabolism and radio-sensitivity of the respective ovarian cancer-derived cell lines.We found that all three inhibitors tested led to significant changes in the tumor cell energy metabolism at non-cytotoxic concentrations. Furthermore, we found that inhibition of tumor glycolysis by 2-deoxy-D-glucose in combination with rotenone decreased the radio-resistance at a clinically relevant radiation dose. This apparent radio-sensitizing effect appears to be based on an increased level of double strand DNA breaks 1 h and 24 h after gamma irradiation. Both cancer-derived cell lines maintained their metabolic properties, as well as their protein expression profiles and levels of reactive oxygen species in xenografts, thus providing a suitable model system for further in vivo investigations.A combination of metabolic inhibitors and reactive oxygen species-generating therapies, such as irradiation, may effectively enhance the therapeutic response in particularly metabolically highly active (ovarian) tumors.
Starting Page	377
Ending Page	385
Page Count	9
File Format	PDF
ISSN	22113428
Journal	Cellular Oncology
Volume Number	38
Issue Number	5
e-ISSN	22113436
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-08-19
Publisher Institution	International Society for Cellular Oncology
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Tumor metabolism Radiation therapy Metabolic inhibitors Ovarian cancer imBI Cancer Research Biomedicine general Pathology Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Molecular Medicine Oncology

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