Sodium butyrate induces apoptosis of human colon cancer cells by modulating ERK and sphingosine kinase 2.
OBJECTIVE
To investigate the role of extracellular signal-regulated kinase (ERK) in apoptosis of human colon cancer (HCT116) cells.


METHODS
After 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.


RESULTS
The 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.


CONCLUSIONS
ERK 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.
Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China; Department of Clinical Laboratory, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong, China.
Min
M
Xiao
Department of Toxicology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China.
Yun Gang
YG
Liu
Department of Endocrinology, Nanfang Hospital, Guangzhou 510515, Guangdong, China.
Meng Chen
MC
Zou
Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China.
Fei
F
Zou
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020148:Butyric Acid / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D045325:HCT116 Cells / Q000187:drug effects; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D000099157:Sphingosine Kinase
D020148:Butyric Acid; D048049:Extracellular Signal-Regulated MAP Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011493:Protein Kinase C; D034741:RNA, Small Interfering; D000099157:Sphingosine Kinase; C089212:protein kinase D
Apoptosis; Colon caner; ERK; Sodium butyrate; Sphingosine kinase 2