BROWN ALGAE Hizikia fusiforme INDUCES CASPASE-DEPENDENT APOPTOSIS IN HUMAN LEUKEMIA

Hizikia fusiforme is an edible brown seaweed, which is widely distributed in the coastal areas of Korea, Japan, and China. It is broadly used as an Oriental herbal medicine. A recent study reported that H. fusiforme contains a number of compounds possessing anti-inflammatory, anti-oxidant and anticoa-gulant proprieties. Hizikia fusiforme is renowned for the possession of anti-inflammatory and anti-oxidant properties. In this study, the role of the ethyl alcohol extract of H. fusiforme (EAHF) in the induction of apoptosis in human leukemia U937 cells was investigated.

Protein expression was investigated by Western blot analysis. Cell viability and apoptosis were analyzed by an MTT assay and flow cytometric analysis. Caspase activity was analyzed using a caspase-specific kit.

EAHF suppressed the proliferation of U937 cells in a dose-dependent manner. This effect was closely related to the induction of apoptosis via the downregulation of IAP family members such as IAP-1, IAP-2 and XIAP, as well as Bcl-2 proteins. The results also showed that caspases play an essential role in EAHF-induced apoptosis by generating of reactive oxygen species (ROS). In addition, ROS scavenging by N-acetyl-L-cysteine (NAC) and glutathione (GSH) decreased EAHF-induced apoptosis via the suppression of caspase activity. Although EAHF induced the phosphorylation of mitogen-activated protein kinases (MAPKs), treatment with MAPK inhibitors did not affect EAHF-induced apoptosis. These results suggest that EAHF induces apoptosis in U937 cells via ROS-dependent caspase activation.

Keywords: Hizikia fusiforme, Apoptosis, Caspase, Reactive oxygen species