Streptochlorin is a small molecule that produced by marine Streptomyces sp. that is known to have anti-angiogenic and anti-
cancer properties. However, the mechanism by which
streptochlorin functions is not well understood. In this study, we investigated the pro-apoptotic effect of
streptochlorin in human leukemic U937 cells.
Streptochlorin treatment resulted in concentration- and time-dependent growth inhibition by inducing apoptosis. The increase in apoptosis that was induced by
streptochlorin was correlated with down-regulation of anti-apoptotic Bcl-2 expression, up-regulation of pro-apoptotic Bax and FasL, a decrease in the mitochondrial membrane potential (
MMP), activation of
caspases and degradation of
poly-(ADP-ribose)polymerase and
phospholipase C-gamma1
protein. In addition, the cytotoxic effects and apoptotic characteristics induced by
streptochlorin were significantly inhibited by
z-DEVD-fmk, a
caspase-3 inhibitor, which demonstrates the important role that
caspase-3 played in the process. Furthermore, Bcl-2 overexpression significantly reversed the
streptochlorin-induced growth inhibitory effects via inhibition of the
MMP collapse and
caspases activation and effectively attenuated the apoptotic response to
streptochlorin. However, the elevated levels of FasL expression induced by
streptochlorin were not reduced by Bcl-2 overexpression. Taken together, these findings demonstrate that the pro-apoptotic effect of
streptochlorin is mediated through activation of
caspases and mitochondria in U937 cells.