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标题：Central Role of Cell Cycle Regulation in the Antitumoral Action of Ocoxin
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作者：Javier Pérez-Peña ; Elena Díaz-Rodríguez ; Eduardo Sanz 等
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2019
卷号：11
期号：5
页码：1068-1079
DOI：10.3390/nu11051068
出版社：MDPI Publishing
摘要：Nutritional supplements which include natural antitumoral compounds could represent safe and efficient additives for cancer patients. One such nutritional supplement, Ocoxin Oral solution (OOS), is a composite formulation that contains several antioxidants and exhibits antitumoral properties in several in vitro and in vivo tumor conditions. Here, we performed a functional genomic analysis to uncover the mechanism of the antitumoral action of OOS. Using in vivo models of acute myelogenous leukemia (AML, HEL cells, representative of a liquid tumor) and small-cell lung cancer (GLC-8, representative of a solid tumor), we showed that OOS treatment altered the transcriptome of xenografted tumors created by subcutaneously implanting these cells. Functional transcriptomic studies pointed to a cell cycle deregulation after OOS treatment. The main pathway responsible for this deregulation was the E2F–TFDP route, which was affected at different points. The alterations ultimately led to a decrease in pathway activation. Moreover, when OOS-deregulated genes in the AML context were analyzed in patient samples, a clear correlation with their levels and prognosis was observed. Together, these data led us to suggest that the antitumoral effect of OOS is due to blockade of cell cycle progression mainly caused by the action of OOS on the E2F–TFDP pathway.
关键词：small-cell lung cancer; acute myeloid leukemia; antioxidants; cell cycle; p27; apoptosis small-cell lung cancer ; acute myeloid leukemia ; antioxidants ; cell cycle ; p27 ; apoptosis