Sodium butyrate induces apoptosis of human colon cancer cells by modulating ERK and sphingosine kinase 2.

Min Xiao; Yun Gang Liu; Meng Chen Zou; Fei Zou

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Sodium butyrate induces apoptosis of human colon cancer cells by modulating ERK and sphingosine kinase 2.

Author: Min XIAO ^{1
,

2} ; Yun Gang LIU ³ ; Meng Chen ZOU ⁴ ; Fei ZOU ⁵
Author Information

1. Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China
2. Department of Clinical Laboratory, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong, China.
3. Department of Toxicology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China.
4. Department of Endocrinology, Nanfang Hospital, Guangzhou 510515, Guangdong, China.
5. Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China.
Publication Type:Journal Article
Keywords: Apoptosis; Colon caner; ERK; Sodium butyrate; Sphingosine kinase 2
MeSH: Apoptosis; drug effects; physiology; Butyric Acid; pharmacology; Extracellular Signal-Regulated MAP Kinases; metabolism; HCT116 Cells; drug effects; Humans; Phosphotransferases (Alcohol Group Acceptor); genetics; metabolism; Protein Kinase C; genetics; metabolism; RNA, Small Interfering; Signal Transduction; drug effects
From: Biomedical and Environmental Sciences 2014;27(3):197-203
CountryChina
Language:English
Abstract:
OBJECTIVETo investigate the role of extracellular signal-regulated kinase (ERK) in apoptosis of human colon cancer (HCT116) cells.
METHODSAfter the HCT116 cells were pretreated with specific ERK inhibitor (U0126) or specific siRNA and exposed to 10 mmol/L sodium butyrate (NaBT) for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy.
RESULTSThe U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the U0126-blocked export of SphK2.
CONCLUSIONERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.