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
