title: Lower salinomycin concentration increases apoptotic detachment in high-density cancer cells.
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 &mu;M 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 &mu;M Sal treatment resulted in fewer attached cells than that of the 5 &mu;M 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 &mu;M Sal increased cellular detachment of newly produced daughter cells. The easily-detachable cells were undergoing apoptosis. It seems that the 0.5 &mu;M 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.
authors.affiliation: Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do 410-769, Korea. yoons@ncc.re.kr.
authors.forename: Ju-Hwa
authors.initials: JH
authors.lastname: Kim
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Kim
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Suntaek
authors.initials: S
authors.lastname: Hong
authors.forename: Sungpil
authors.initials: S
authors.lastname: Yoon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D011714:Pyrans / Q000494:pharmacology*; D013997:Time Factors; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides