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

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

  • Biochem Biophys Res Commun. 2018 Jul 7;502(1):110-115. doi: 10.1016/j.bbrc.2018.05.129.
Xing Shen 1,  Shuang Xing 2,  Lu Zhang 3,  Fangmin Wang 4,  Hongling Ou 5,  Yajun Shan 2,  He Xiao 6,  Guolin Xiong 2,  Xinru Wang 5,  Qinshi Zhao 7,  Yuwen Cong 8,  Zuyin Yu 9
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China. Electronic address: shen_xingjyk@163.com.
  • 2 Department of Pathophysiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China.
  • 3 Department of Pathophysiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China; Department of Clinical Laboratory, The General Hospital of PLA Rocket Force, Beijing, China.
  • 4 Department of Graduates, Anhui Medical University, Hefei, China.
  • 5 Department of Clinical Laboratory, The General Hospital of PLA Rocket Force, Beijing, China.
  • 6 Department of Molecular Immunology, Institute of Pharmacology and Toxicology, Beijing, China.
  • 7 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
  • 8 Department of Pathophysiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China. Electronic address: congyw@nic.bmi.ac.cn.
  • 9 Department of Pathophysiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China; Department of Graduates, Anhui Medical University, Hefei, China. Electronic address: yuzy79@163.com.
PMID: 29787755 DOI: 10.1016/j.bbrc.2018.05.129
Abstract

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.

Keywords

Differentiation; Lyn; Protein kinase C; Tyrosine kinase inhibitor; Vibsanin A.

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