Apoptosis induced by nucleosides in the human hepatoma HepG2.
OBJECTIVE
To investigate the apoptotic effects of nucleosides on the human hepatoma HepG2.


METHODS
The nucleosides included inosine (I), cytidine (C), uridine (U), thymidine (T), adenosine (A), and guanosine (G). Cells were incubated by the mediums with or without nucleosides at 37 degree C in a 50 mL/L CO(2) humidified atmosphere.


RESULTS
It was found that the cell viabilities were significantly decreased, when cells were treated with 30 mmol/L I, 30 mmol/L C, 30 mmol/L U, 30 mmol/L T, 0.5 mmol/L A, and 0.5 mmol/L G after 12 h incubation (P< 0.05). About the apoptotic phenomenon, the cell percentages of sub-G(1) cells were significantly increased in the mediums containing nucleosides such as C, U, T, A, and G (P< 0.05). Furthermore, the caspase-3 activity was increased, when the cells were incubated with T (P< 0.05). The protein expressions of p53 and p21 showed no difference in each group. To investigate the mechanism of apoptosis induced by nucleosides, it was found that the contents of soluble Fas ligand contents were increased in HepG2 cells following I, U, T, and A treatment (P< 0.05). But, TNF-alpha and cytochrome c were undetectable.


CONCLUSIONS
Thymidine may induce the apoptosis in HepG2, but the effective dosages and reactive time must be investigated in the future study. However, the apoptosis-inducing abilities of other nucleosides were still unclear in this study.
Yang
Suh-Ching
SC
School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei 110, Taiwan, China.
Chiu
Che-Lin
CL
Huang
Chi-Chang
CC
Chen
Jiun-Rong
JR
D017209:Apoptosis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002470:Cell Survival; D053222:Fas Ligand Protein; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009705:Nucleosides / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D048069:Tumor Necrosis Factors / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D009705:Nucleosides; D048069:Tumor Necrosis Factors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases