Abstract
Identifying novel differentiating agents to promote leukemia-cell differentiation is a pressing need. Here, we demonstrated that vibsanol A, a vibsane-type diterpenoid, inhibited the growth of acute myeloid leukemia (AML) cells via induction of cell differentiation, which was characterized by G1 cell cycle arrest. The differentiation-inducing effects of vibsanol A were dependent upon protein kinase C (PKC) activation, and subsequent activation of the extracellular signal-regulated kinase (ERK) pathway. Furthermore, vibsanol A treatment increased reactive oxygen species (ROS) levels, and the ROS scavenger NAC reversed the vibsanol A-induced cell differentiation, indicating an important role for ROS in the action of vibsanol A. Finally, vibsanol A exhibited a differentiation-enhancing effect when used in combination with all-trans retinoic acid in AML cells. Overall results suggested that vibsanol A induces AML cell differentiation via activation of the PKC/ERK signaling and induction of ROS. Vibsanol A may prove to be an effective differentiating agent against AML.
Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China [81273544] and the Chinese Science and Technology Major Projects [2012ZX09102201-003].
Potential conflict of interest
Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1421754.