A newly synthesized dithiocarbamate derivative, 4-methylpiperazine-1-carbodithioc-acid-3-cyano-3,3-diphenylpropyl
ester hydrochloride (
TM208), has demonstrated anticancer effects with low toxicity in earlier studies; however, the mechanism has yet to be identified. We explored antitumor effects of
TM208 and the possible mechanisms by which it inhibited the growth of human
hepatocellular carcinoma cell line QGY-7703 xenograft
tumors. Cell proliferation was evaluated with the
sulforhodamine B assay in vitro. The results suggested that
TM208 had slightly antiproliferative activity on QGY-7703 cells. The antitumor effect of
TM208 was assessed in nude mice xenografted with QGY-7703
tumors. We found that
TM208 significantly inhibited
tumor growth but did not cause loss of
body weight or
leukocytopenia. Western blotting was used to detect the expression of
protein kinase C alpha,
mitogen-activated protein kinase signal pathways, and cell cycle-related
proteins. The results showed that
TM208 decreased the expression of
protein kinase C alpha, phospho-
extracellular signal-regulated kinase-1/2, phospho-p38,
cyclin B1, cell division cycle 2 (cdc2), and phospho-cdc2 (Thr161) and increased the expression of phospho-cdc2 (Tyr15). Taken together, our data show that
TM208 has little antiproliferative effect on QGY-7703 cells in vitro, whereas it significantly inhibits the growth of QGY-7703 xenograft
tumors with low toxicity in vivo. The inhibition of
mitogen-activated protein kinase signal pathways and the regulation of the G2/M phase may be responsible for its antitumor effects.