Vibsanin A sensitizes human acute myeloid leukemia cells to tyrosine kinase inhibitor-induced myeloid differentiation via activation of PKC and upregulation of Lyn

Differentiation therapies have been proposed to overcome the impaired cell differentiation in acute myeloid leukemia (AML). However, thus far the all-trans retinoic acid-based differentiation therapy has been the only successful modality in treating acute promyelocytic leukemia. Here, we showed that vibsanin A, a novel protein kinase C (PKC) activator, sensitized AML cells to tyrosine kinase inhibitor (TKI)-induced differentiation. Vibsanin A augmented the ability of TKIs to induce growth inhibition and G1 cell cycle arrest of AML cells. Mechanistically, PKC activation was involved in the differentiation-inducing effects of combining vibsanin A with TKIs. Moreover, we found that vibsanin A enhanced TKI-induced Lyn expression and suppression of Lyn interfered with AML cell differentiation, indicating an essential role for Lyn expression in the combination-induced differentiation. Finally, combining vibsanin A and TKIs enhanced the activation of the Raf/MEK/ERK cascade. Together, this is the first study to evaluate the synergy of vibsanin A and TKIs in AML cell differentiation. Our study lays the foundation in assessing new opportunities for the combination of vibsanin A and TKIs as a promising approach for future differentiation therapy. •Vibsanin A sensitizes AML cells to tyrosine kinase inhibitor (TKI)-induced differentiation.•Both PKC activation and Lyn induction contribute to combination-induced AML cell differentiation.•The combination treatment enhanced the activation of the Raf/MEK/ERK cascade.•Vibsanin A coupled with TKIs may lead to new applications of differentiation-based approaches for AML.