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Int. J. Mol. Sci. 2013, 14(9), 17304-17318;

Low Amount of Salinomycin Greatly Increases Akt Activation, but Reduces Activated p70S6K Levels

Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do 410-769, Korea
College of Pharmacy, Sookmyung Women's University, Seoul 140-133, Korea
School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea
Author to whom correspondence should be addressed.
Received: 8 July 2013 / Revised: 12 August 2013 / Accepted: 13 August 2013 / Published: 22 August 2013
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
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The present study identified a novel salinomycin (Sal)-sensitization mechanism in cancer cells. We analyzed the signal proteins Akt, Jnk, p38, Jak, and Erk1/2 in cancer cell lines that had arrested growth following low amounts of Sal treatment. We also tested the signal molecules PI3K, PDK1, GSK3β, p70S6K, mTOR, and PTEN to analyze the PI3K/Akt/mTOR pathway. The results showed that Sal sensitization positively correlates with large reductions in p70S6K activation. Interestingly, Akt was the only signal protein to be significantly activated by Sal treatment. The Akt activation appeared to require the PI3K pathway as its activation was abolished by the PI3K inhibitors LY294002 and wortmannin. The Akt activation by Sal was conserved in the other cell lines analyzed, which originated from other organs. Both Akt activation and C-PARP production were proportionally increased with increased doses of Sal. In addition, the increased levels of pAkt were not reduced over the time course of the experiment. Co-treatment with Akt inhibitors sensitized the Sal-treated cancer cells. The results thereby suggest that Akt activation is increased in cells that survive Sal treatment and resist the cytotoxic effect of Sal. Taken together; these results indicate that Akt activation may promote the resistance of cancer cells to Sal. View Full-Text
Keywords: Salinomycin; Akt; p70S6K; mTOR; LY294002; wortmannin; cancer Salinomycin; Akt; p70S6K; mTOR; LY294002; wortmannin; cancer
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Kim, J.-H.; Choi, A.-R.; Kim, Y.K.; Kim, H.S.; Yoon, S. Low Amount of Salinomycin Greatly Increases Akt Activation, but Reduces Activated p70S6K Levels. Int. J. Mol. Sci. 2013, 14, 17304-17318.

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