Tryptanthrin, a kind of
indole quinazoline alkaloid, has been shown to exhibit anti-microbial, anti-
inflammation and anti-
tumor effects both in vivo and in vitro. However, its
biological activity on human
chronic myeloid leukemia cell line K562 is not fully understood. In the present study, we investigated the proliferation-attenuating and apoptosis-inducing effects of
tryptanthrin on
leukemia K562 cells in vitro and explored the underlying mechanisms. The results showed that
tryptanthrin could significantly inhibit K562 cells proliferation in a time- and dose-dependent manner as evidenced by MTT assay and flow cytometry analysis. We also observed pyknosis,
chromatin margination and the formation of apoptotic bodies in the presence of
tryptanthrin under the electron microscope. Nuclei fragmentation and condensation by
Hoechst 33258 staining were detected as well. The amount of apoptotic cells significantly increased whereas the mitochondrial membrane potential decreased dramatically after
tryptanthrin exposure. K562 cells in the
tryptanthrin treated group exhibited an increase in cytosol cyt-c, Bax and activated
caspase-3 expression while a decrease in Bcl-2, mito cyt-c and
pro-caspase-3 contents. However, the changes of
pro-caspase-3 and activated
caspase-3 could be abolished by a pan-
caspase inhibitor
ZVAD-FMK. These results suggest that
tryptanthrin has proliferation-attenuating and apoptosis-inducing effects on K562 cells. The underlying mechanism is probably attributed to the reduction in mitochondria membrane potential, the release of mito cyt-c and
pro-caspase-3 activation.