Radiosensitization of prostate cancer cells by 2-deoxyglucose

Rae, C. , Sey, C.H.C. and Mairs, R.J. (2018) Radiosensitization of prostate cancer cells by 2-deoxyglucose. Madridge Journal of Oncogenesis, 2(1), pp. 30-34.

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Abstract

Prostate cancer is the most common malignancy of men. Treatment options include radiotherapy with or without hormonal manipulation and radical prostatectomy. However, there is no effective treatment for disseminated disease. A hallmark of malignancy is abnormal metabolism which also confers survival advantages and contributes to resistance to therapy. In response to exposure to ionizing radiation, metabolic pathways are activated which can protect the cell from irreversible injury. Tumor cell glycolytic activity is elevated and correlates with aggressiveness and radio resistance, indicating that targeting glucose metabolism may sensitize cancer cells to radiation. We have demonstrated that the clonogenic kill of PC3 cells induced by exposure to x-rays was enhanced by the glycolytic inhibitor 2-deoxyglucose (2DG). In contrast, treatment with 2DG failed to inhibit growth of multicellular spheroids derived from LNCaP cells. However, 2DG treatment, in the absence of irradiation, induced similar toxicity to PC3 and LNCaP cells cultured as monolayers. Radiation-induced cell cycle arrest was prevented by the simultaneous administration of 2DG in both cell lines, indicating a possible mechanism underlying sensitization. Therefore, we hypothesise that observed differences in cellular response to incubation with 2DG in the presence or absence of ionizing radiation resulted from variation in metabolic processes between tumor cell types. We conclude that inhibition of glucose metabolism by 2DG is an effective method for sensitizing prostate cancer cells to experimental radiotherapy and that this may occur by preventing DNA repair during radiation-induced cell cycle arrest.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mairs, Professor Robert and Rae, Dr Colin
Authors: Rae, C., Sey, C.H.C., and Mairs, R.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Madridge Journal of Oncogenesis
Publisher:Madridge Publishers
Copyright Holders:Copyright © 2018 Rae C et al.
First Published:First published in Madridge Journal of Oncogenesis 291): 30-34
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
743801Targeted radiotherapy of prostate cancer with drugs exploiting the aberrant metabolism of tumoursRobert MairsChief Scientist office (CSO)TCS/16/38ICS - EPIGENETICS