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Lower Salinomycin Concentration Increases Apoptotic Detachment in High-Density Cancer Cells
Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do 410-769, Korea
Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Korea
Department of Systems Biology, Yonsei University, Seoul 120-749, Korea
College of Pharmacy, Pusan National University, Busan 609-390, Korea
* Author to whom correspondence should be addressed.
Received: 7 September 2012; in revised form: 28 September 2012 / Accepted: 9 October 2012 / Published: 12 October 2012
Abstract: The present study identified a novel salinomycin (Sal) sensitization mechanism in cancer. We tested whether Sal reduced proliferation in a high-density population by counting attached cell numbers after Sal treatment. Sal reduced proliferation in high-density cell populations. Longer exposure to Sal further reduced proliferation. Sal concentrations of 0.1 and 5 μM had similar sensitization effects, suggesting that Sal toxicity was minimal with longer exposure to a high-density cell population. The results suggest that Sal can be applied at a relatively low concentration for a longer time to overcome drug-resistant solid tumors. The 0.5 μM Sal treatment resulted in fewer attached cells than that of the 5 μM Sal treatment with a longer exposure. The lower Sal concentration mainly increased the number of easily detachable cells on the surface. In particular, 0.5 μM Sal increased cellular detachment of newly produced daughter cells. The easily-detachable cells were undergoing apoptosis. It seems that the 0.5 μM Sal treatment also increased cellular toxicity. These novel findings may contribute to the development of Sal-based therapy for patients with drug-resistant cancer or a high-density solid tumor.
Keywords: salinomycin; apoptosis; high cell density; spaces among cells; cellular detachment; lower concentration
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Kim, J.-H.; Kim, T.Y.; Kim, H.S.; Hong, S.; Yoon, S. Lower Salinomycin Concentration Increases Apoptotic Detachment in High-Density Cancer Cells. Int. J. Mol. Sci. 2012, 13, 13169-13182.
Kim J-H, Kim TY, Kim HS, Hong S, Yoon S. Lower Salinomycin Concentration Increases Apoptotic Detachment in High-Density Cancer Cells. International Journal of Molecular Sciences. 2012; 13(10):13169-13182.
Kim, Ju-Hwa; Kim, Tae Y.; Kim, Hyung S.; Hong, Suntaek; Yoon, Sungpil. 2012. "Lower Salinomycin Concentration Increases Apoptotic Detachment in High-Density Cancer Cells." Int. J. Mol. Sci. 13, no. 10: 13169-13182.