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KMID : 1140120100150030185
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Cancer Prevention Research
2010 Volume.15 No. 3 p.185 ~ p.189
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Effects of Celecoxib and Compound C on AMPKα1/Akt Signaling in MCF-7 Breast Cancer Cells
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Lee Yun-Kyoung
Park Song-Yi
Lee Sol-Hwa
Kim Young-Min
Park Ock-Jin
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Abstract
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Most breast cancers have characteristics of over-activated Akt, a major stimulator of cell growth and tumor progression. Thus, suppressing Akt activity can provide an effective way for tumor control. In this study, we have focused on the regulatory effects of AMPKα1 and cyclooxygenase-2 (COX-2) on cell survival signal in MCF-7 breast cancer cells using their specific inhibitors, Compound C and Celecoxib for AMPKα1 and COX-2, respectively. Our results showed that the inhibition of AMPKα1 by Compound C increased both Akt and COX-2 levels. Blocking COX-2 expression by Celecoxib increased AMPKα1, and surprisingly it increased Akt in MCF-7 cells. To determine the relationship between Akt and COX-2 signals, we used the cox-2 negative and positive cells. In cox-2 positive cells, Celecoxib decreased COX-2 level as well as Akt activity, but activated AMPKα1. In addition, treatment of Celecoxib and LY294002, Akt inhibitor reduced cell growth of MCF-7 cells. Therefore, these results suggest that there might be existence in mutual regulatory interactions between COX-2 and Akt signals in only cancerous applicable cells. Moreover, AMPKα1 can act as a negative regulator of Akt and COX-2 signals, and targeting AMPKα1 to control tumor growth can be an effective way due to its inhibitory
effects of Akt against breast cancers.
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KEYWORD
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Akt, AMP-activated protein kinase, Celecoxib, Compound C, Cyclooxygenase-2
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