PURPOSE:
Zinc is one of the
trace minerals in the body and is known to have an anticancer effect by inducing
apoptosis in
prostate cancer. We aimed to investigate the antiproliferative effects of a
zinc-
citrate compound in
bladder cancer. MATERIALS AND
METHODS:
A
bladder cancer cell line (MBT-2) was treated with a
zinc-
citrate compound at different
time intervals and concentrations. Mitochondrial (m)-
aconitase activity was determined by use of the
aconitase assay.
DNA laddering
analysis was performed to investigate
apoptosis of MBT-2
cells. The molecular mechanism of
apoptosis was investigated by
Western blot analysis of p53, p21waf1, Bcl-2, Bcl-xL, and Bax and also by
caspase-3 activity
analysis.
RESULTS:
Treatment with the
zinc-
citrate compound resulted in a
time- and
dose-dependent decrease in
cell number of MBT-2
cells. M-
aconitase activity was significantly decreased.
DNA laddering
analysis indicated
apoptosis of MBT-2
cells. The
zinc-
citrate compound increased the expression of p21waf1 and p53 and reduced the expression of Bcl-2 and Bcl-xL
proteins but induced expression of
Bax protein. The
zinc-
citrate compound induced
apoptosis of MBT-2
cells by activation of the
caspase-3 pathway.
CONCLUSIONS:
We have shown that a
zinc-
citrate compound induces apoptotic
cell death in a
bladder cancer cell line, MBT-2, by
caspase-3 activation through
up-regulation of apoptotic
proteins and
down-regulation of antiapoptotic
proteins.