Effects of diethyldithiocarbamate on proliferation, redifferention, and apoptosis in human hepatoma cells.
OBJECTIVE
To examine the effects of diethyldithiocarbamate (DDC) on the proliferation, redifferentiation, and apoptosis in human hepatoma cells.


METHODS
Cell surface charge, biochemical changes, cell growth in soft agar, single cell electrophoresis, electron microscopy examination, and flow cytometry analysis were measured.


RESULTS
After being treated with DDC 3 mmol/L the growth curve and mitotic index of human hepatoma cells decreased remarkably, and the cellular growth inhibitory rate amounted to 52.4 %. The indices related with cell malignancy were alleviated significantly, such as the cell surface charge decreased significantly, the electrophoresis rate dropped from 1.6 to 0.8 micron . s-1 . V-1 . cm-1, the average value of alpha-fetoprotein (alpha-FP) content decrease d from 314 to 95 microg/g (protein), and gamma-glutamyl-transpeptidase (gamma-GT) activity from 0.9 to 0.14 U/g (protein). The cell differentiation index increased significantly, such as the average levels of tyrosine-alpha-ketoglutarate transaminase (TAT) activity increased from 11.6 to 36 micromol/g (protein), and the colonogenic potential decreased by 95.6 %. The apoptotic bodies, detached cells, and apoptotic morphological features appeared, and the treated cells DNA was fragmented as observed by the comet assay. The flow cytometric results showed that a 42.9 % fractional DNA content existed in the treated cells.


CONCLUSIONS
DDC can inhibit human hepatoma cells proliferation, and can induce redifferentiation as well as apoptosis.
Kang
J H
JH
School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
Wei
Y M
YM
Zheng
R L
RL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004050:Ditiocarb / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D004050:Ditiocarb