Rosemary (Rosmarinus officinalis), a culinary spice and medicinal herb, has been widely used in European
folk medicine to treat numerous ailments. Many studies have shown that rosemary extracts play important roles in anti-
inflammation, anti-
tumor, and anti-proliferation in various in vitro and in vivo settings. The roles of
tumor suppression of rosemary have been attributed to the major components, including
carnosic acid,
carnosol, and
rosmarinic acid,
rosmanol, and
ursolic acid. This study was to explore the effect of
rosmanol on the growth of COLO 205 human colorectal
adenocarcinoma cells and to delineate the underlying mechanisms. When treated with 50 μM of
rosmanol for 24h, COLO 205 cells displayed a strong apoptosis-inducing response with a 51% apoptotic ratio (IC(50) ∼42 μM).
Rosmanol increased the expression of Fas and FasL, led to the cleavage and activation of
pro-caspase-8 and Bid, and mobilized Bax from cytosol into mitochondria. The mutual activation between tBid and Bad decreased the mitochondrial membrane potential and released
cytochrome c and
apoptosis-inducing factor (AIF) to cytosol. In turn,
cytochrome c induced the processing of
pro-caspase-9 and
pro-caspase-3, followed by the cleavage of
poly-(ADP-ribose) polymerase (PARP) and DNA fragmentation factor (DFF-45). These results demonstrate that the
rosmanol-induced apoptosis in COLO 205 cells is involvement of
caspase activation and involving complicated regulation of both the mitochondrial apoptotic pathway and
death receptor pathway.