An ent-Kaurane Diterpenoid Isolated from Rabdosia excisa Suppresses Bcr-Abl Protein Expression in Vitro and in Vivo and Induces Apoptosis of CML Cells.

Chronic myelogenous leukemia (CML) is a disease of the blood stem cells that features the oncoprotein Bcr-Abl. Tyrosine kinase inhibitors (TKIs) are used to treat CML patients, but these have limited efficacy due to the emergence of resistance via genetic mutation. Kamebakaurin is an ent-kaurane diterpenoid that has been isolated from Rabdosia excisa (Maxim.) H.Hara. Herein, we investigate the potential of kamebakaurin as a chemotherapy reagent for the treatment of CML. We conducted in vitro and in vivo biological experiments and found that kamebakaurin potently inhibits cell proliferation, mainly by enhancing cell apoptosis and down-regulating Bcr-Abl protein levels. In addition, kamebakaurin was found to inhibit tumor growth and has no side effects on five internal organs for in vivo experiment. These results suggest that kamebakaurin is a potential anticancer agent and is a key compound for further investigations.