Colorectal cancer remains often refractory to classic
therapies. In consequence, the search for new anti-
tumor agents with minimal toxicity is of particular interest in
colon cancer treatment.
Prodigiosin as a secondary metabolite of Serratia marcescens induces apoptosis in various kinds of
cancer cells with low toxicity on normal cells. In the present study, we evaluated the effect of
prodigiosin on proliferation and expression of apoptotic-related genes in HT-29 cells. Malignant cells were treated to various concentrations of
prodigiosin and proliferation rate,
survivin, Bcl-2, Bax and Bad
mRNA levels,
caspase 3 activation and apoptosis were evaluated by different cellular and molecular techniques. Treatment of cells with increasing concentration of
prodigiosin decreased significantly cell proliferation in a dose- and time-dependent manner. Following 48-h treatment, growth rate was measured to be 77 ± 6.8, 41.3 ± 3.1 and 46 ± 6.3 % for 100, 400 and 600 nM
prodigiosin, respectively, compared to untreated cells. This molecule induced 61.7, 90 and 89 % decrease in
survivin mRNA level as well as 1.9-, 2.8- and 2.2-fold increase in
caspase 3 activation for indicated concentrations of
prodigiosin, respectively. The level of Bcl-2
mRNA was inversely proportional to Bax and Bad
mRNA levels. Low
mRNA levels of Bcl-2 combined with high levels of Bax and Bad mRNAs were correlated to higher apoptosis rate in treated cells. Our data suggest that
prodigiosin-induced apoptosis may ascribe to Bcl-2 and
survivin inhibition in HT-29 cells and these genes may provide promising molecular targets of
prodigiosin. Collectively,
prodigiosin may have a great potential for
colorectal cancer-directed
therapy.