Embelin is a Nonpeptidic XIAP Inhibitor

Embelin is an inhibitor of X-linked inhibitor of apoptosis protein (XIAP). It derives from the fruit of Embelia ribes. Embelin also possess therapeutic properties, such as anticancer, antioxidant, anti-inflammation, antidiabetes, and antihelminthic qualities.

XIAP is the most potent member of the inhibitors of apoptosis proteins (IAP) gene family. It binds and inhibits caspase. Therefore, XIAP inhibits cell migration and invasion and induces apoptosis. Morever, Embelin, as an antitumor agent has the potential to induce cell growth inhibition and apoptosis in different human cancers.

Embelin is an active ingredient of traditional herbal remedies for cancer and other diseases. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers.

In this article, we will introduce an anti-cancer agent Embelin.

Embelin (Embelic acid) is a potent inhibitor of nonpeptidic XIAP with an IC₅₀ of 4.1 μM. This compound inhibits cell growth, induces apoptosis, and activates caspase-9 in prostate cancer cells with high levels of XIAP. It also blocks NF-kappaB signaling pathway leading to suppression of NF-kappaB-regulated antiapoptotic and metastatic gene products. Embelin also induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells.

Embelin (0-300 μM) potently induces OSCC cell death. Treatment with Embelin also results in morphological and biochemical changes associated with apoptosis. Furthermore, Embelin reduces MMP and induces the degradation of caspase-9, caspase-3, and ICAD, and it also produces a processed ICAD 20 kDa and PARP 85 kDa fragments dose-dependently.

In conclusion, Embelin induces apoptosis and autophagy in Ca9–22 cells. As Embelin clearly can induce autophagy and is involved in the survival of Ca9–22 cells, the combination of Embelin and an effective autophagy inhibitor could be a potentially useful therapy for oral cancer research. Meanwhile, the identification of the molecular mechanism by which Embelin acts will provide useful information for its development as a novel anti-cancer agent for the management of Ca9–22.

Reference:

Lee YJ, et al. XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells.

Ahn KS, et al. Embelin, an inhibitor of X chromosome-linked inhibitor-of-apoptosis protein, blocks nuclear factor-kappaB (NF-kappaB) signaling pathway leading to suppression of NF-kappaB-regulated antiapoptotic and metastatic gene products.

Nikolovska-Coleska Z, et al. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database.