NDLI: PTEN-regulated AKT/FoxO3a/Bim signaling contributes to reactive oxygen species-mediated apoptosis in selenite-treated colorectal cancer cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Luo, H. Yang, Y. Duan, J. Wu, P. Jiang, Q. Xu, C.
Description	Country affiliation: China Author Affiliation: Luo H ( National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, China.)
Abstract	Mounting evidence shows that selenium possesses chemotherapeutic potential against tumor cells, including leukemia, prostate cancer and colorectal cancer (CRC) cells. However, the detailed mechanism by which sodium selenite specifically kills tumor cells remains unclear. Herein, we demonstrated that supranutritional doses of selenite-induced apoptosis in CRC cells through reactive oxygen species (ROS)-dependent modulation of the PI3K/AKT/FoxO3a signaling pathway. First, we found that selenite treatment in HCT116 and SW480 CRC cells caused inhibition of AKT and the nuclear accumulation of FoxO3a by western blot and immunofluorescence analyses, respectively, thereby facilitating transcription of the target genes bim and PTEN. Modulation of the AKT/FoxO3a/Bim signaling pathway by chemical inhibitors or RNA interference revealed that these events were critical for selenite-induced apoptosis in CRC cells. Additionally, we discovered that FoxO3a-mediated upregulation of PTEN exerted a further inhibitory effect on the AKT survival pathway. We also corroborated our findings in vivo by performing immunohistochemistry experiments. In summary, our results show that selenite could induce ROS-dependent FoxO3a-mediated apoptosis in CRC cells and xenograft tumors through PTEN-mediated inhibition of the PI3K/AKT survival axis. These results help to elucidate the molecular mechanisms underlying selenite-induced cell death in tumor cells and provide a theoretical basis for translational applications of selenium.
File Format	HTM / HTML
e-ISSN	20414889
DOI	10.1038/cddis.2013.3
Journal	Cell Death and Disease
Volume Number	4
Language	English
Publisher	Nature Publishing Group
Publisher Date	2013-02-07
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Research Support, Non-u.s. Gov't Reactive Oxygen Species Immunoprecipitation Antagonists & Inhibitors Colorectal Neoplasms Genetics Proto-oncogene Proteins C-akt Hct116 Cells Phosphatidylinositol 3-kinases Signal Transduction Rna, Small Interfering Proto-oncogene Proteins Sodium Selenite Pharmacology Metabolism Drug Effects Rna Interference Membrane Proteins Discipline Cell Biology Pten Phosphohydrolase Pathology Apoptosis Regulatory Proteins Up-regulation Cell Line, Tumor Forkhead Transcription Factors Apoptosis
Content Type	Text
Resource Type	Article

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