التفاصيل البيبلوغرافية
| العنوان: |
Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: mechanism of cell death. |
| المؤلفون: |
Aft, R.L., Zhang, F.W., Gius, D. |
| المصدر: |
British Journal of Cancer; 9/23/2002, Vol. 87 Issue 7, p805-812, 8p |
| مصطلحات موضوعية: |
DRUG therapy, CANCER |
| مستخلص: |
Nutrient deprivation has been shown to cause cancer cell death. To exploit nutrient deprivation as anti-cancer therapy, we investigated the effects of the anti-metabolite 2-deoxy-D-glucose on breast cancer cells in vitro. This compound has been shown to inhibit glucose metabolism. Treatment of human breast cancer cell lines with 2-deoxy-D-glucose results in cessation of cell growth in a dose dependent manner. Cell viability as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide conversion assay and clonogenic survival are decreased with 2-deoxy-D-glucose treatment indicating that 2-deoxy-D-glucose causes breast cancer cell death. The cell death induced by 2-deoxy-D-glucose was found to be due to apoptosis as demonstrated by induction of caspase 3 activity and cleavage of poly (ADP-ribose) polymerase. Breast cancer cells treated with 2-deoxy-D-glucose express higher levels of Glut1 transporter protein as measured by Western blot analysis and have increased glucose uptake compared to non-treated breast cancer cells. From these results we conclude that 2-deoxy-D-glucose treatment causes death in human breast cancer cell lines by the activation of the apoptotic pathway. Our data suggest that breast cancer cells treated with 2-deoxy-D-glucose accelerate their own demise by initially expressing high levels of glucose transporter protein, which allows increased uptake of 2-deoxy-D-glucose, and subsequent induction of cell death. These data support the targeting of glucose metabolism as a site for chemotherapeutic intervention by agents such as 2-deoxy-D-glucose. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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