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NF-kB is a transcription factor involved in cancer cell growth and survival. The activation of NF-kB can be assessed by monitoring phosphorylation of RelA p65 at Ser-536, which is a surrogate of the NF-kB transcription factor activation. The objective of this study was to determine if the loss of ATP leads to NF-kB deficiency and thus, apoptotic cell death of “bad” cells in ovarian cancer cells. The independent variables were metformin (Met), an anti-diabetic medicine, another compound MinB functionally similar to Met and a glucose transporter inhibitor BAY-876. The dependent variables were the resulting effect of Met and MinB on phosphorylated AMPK at Thr-172 (marker of ATP loss) and RelA p65 at Ser-536 (marker of NF-kB activation). In each experiment, AMPK and RelA phosphorylation were tested by treatment of ovarian cancer cell lines with Met, MinB, BAY-876, Met+BAY-876, MinB+BAY-876. Western blotting was performed to determine the phosphorylation levels of AMPK and RelA p65. For two gels, the process was repeated. In each gel, Met or MinB treatment leads to thicker bands of AMPK-p, indicating decrease in cellular ATP levels following treatments. The effect of Met, MinB, or BAY-876 on RelA p65 was limited. However, co-treatment of Met or MinB with BAY-876 caused strong inhibition of NF-kB, as reflected by reduction in RelA p65-p. These results suggested that ATP deficiency together with inhibition of glucose transport cause inactivation of NK-kB. Future research will be conducted to study the effects of these compounds or their combinations on ovarian cancer cell growth and survival against from apoptosis.
ATP, glucose transporter, AMPK, NF-kB, ovarian cancer
Biological Factors | Chemical Actions and Uses | Chemicals and Drugs | Medicine and Health Sciences
Current Academic Year
Dr. Frank Fang
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