Taurine Enhances Anticancer Activity of Cisplatin in Human Cervical Cancer Cells - Advances in Experimental Medicine and Biology - page 182

study, taurine reduced cell proliferation in hepatic stellate cells (Chen et al. 2004 ) .
Co-treatment of cisplatin with taurine has more decreased cell proliferation than
single treatment of cisplatin or taurine despite the low concentration of cisplatin.
The results of this experiment indicated that the combination of cisplatin with tau-
rine effectively inhibits cell proliferation.
To verify that taurine and/or cisplatin treatment induced apoptosis, we investigated
apoptotic cells by DAPI staining. Increase of apoptosis in cancer cells is one of the
aims of anticancer treatment (Nimmanapalli and Bhalla 2003 ; Bremer et al. 2006 ) .
Anticancer drugs have the effects via induction of apoptosis in various cancer cells
(Yu and Zhang 2004 ). In the present study, in cells treated with taurine and/or cisplatin
for 72 h, apoptotic cells were observed. In co-treatment of cisplatin with taurine, the
incidence of apoptosis was more increased than single treatment of taurine or
cisplatin.
The p53 tumor suppressor protein is closely related to apoptosis. The p53 protein
plays a major role in cellular response to DNA damage and other genomic aberra-
tions. The main mechanisms of p53 are repair of DNA damage, inhibition of cell
cycle via expression of cell cycle-related proteins, and induction of apoptosis
through regulation of apoptosis-related proteins (Maclaine and Hupp 2009 ) .The
p53 is mutated in many cancer cells, and absence of p53 in cancer cells is known to
stimulate the growth of cancer cells (Chène 2001 ). For those reasons, induction of
p53 is important in anticancer activities. Cells were treated with taurine or cisplatin
for 72 h, and expression of p53 was increased compared with control. Similarly, p53
expression was increased in co-treatment of cisplatin with taurine compared with
control. According to the results of this study, induction of apoptosis caused by
treatment of taurine and/or cisplatin was related to p53 expression.
After treatment of taurine and/or cisplatin for 72 h, caspase-9, caspase-7, and
caspase-6 were observed by western blotting. Caspases are a family of cysteine
proteases. Caspase-cascade system plays essential roles in apoptosis, necrosis, and
inflammation (Budihardjo et al. 1999 ; Fan et al. 2005 ). The results indicated that the
treatment of taurine increased caspase-7 and caspase-6 in a dose-dependent manner.
Especially, caspase-6 was highly increased at 20 mM of taurine compared with the
single treatment of cisplatin. But co-treatment of cisplatin with taurine slightly
decreased caspase-7 and caspase-6 compared to single treatment of taurine. In treat-
ment of taurine, caspase-9 was increased regardless of the taurine concentration
compared to control. But co-treatment of cisplatin with taurine does not enhance the
effects. Through this experiment, taurine treatment alone and combination of cis-
platin with taurine caused the processing of procaspases to cleave, and activation of
caspases leads to the induction of apoptosis.
Cisplatin and taurine were treated for 72 h, and expressions of caspase-3 and
PARP were investigated. Caspase-3 is a key factor in apoptosis execution (Porter
and Jänicke 1999 ). The results indicated that caspase-3 was increased after treat-
ment of taurine in a dose-dependent manner. Combined treatment also increased
caspase-3. PARP also induces apoptosis directly (Konopleva et al. 1999 , Hong et al.
2004 ). However, PARP expressions were not changed. Treatment of taurine and/or
cisplatin had no effects on PARP expression. According to the results of this study,