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Synergistic growth inhibition in HL-60 cells by the combination of acyclic retinoid and vitamin K2

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Abstract

Purpose

The aim of this study was to assess the effects of acyclic retinoid (ACR) and vitamin K2 (VK2) in HL-60 cells.

Methods

We used HL-60 cells, and the Trypan Blue dye exclusion method was used for cell proliferation assays. For detection of apoptosis, the Annexin V–binding capacity of treated cells was examined by flow cytometry. To evaluate the cell cycle, we used a FITC BrdU Flow KIT and flow cytometry. Total extracted and equivalent amounts of protein were examined by Western blotting using specific antibodies.

Results

ACR and VK2 dose dependently inhibited the proliferation of HL-60 cells. These two agents in combination synergistically inhibited cell growth and induced apoptosis. VK2 inhibited activation of the Ras/MAPK signaling pathway, and ACR plus VK2 cooperatively inhibited phosphorylation of RXRα and the growth of HL-60 cells. Moreover, ACR and VK2 induced increases in G0/G1 phase HL-60 cells, alone and synergistically in combination.

Conclusion

The synergistic effects of ACR and VK2 on HL-60 cells may provide a novel strategy for treating leukemia.

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Correspondence to Hisashi Tsurumi.

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Kitagawa, J., Hara, T., Tsurumi, H. et al. Synergistic growth inhibition in HL-60 cells by the combination of acyclic retinoid and vitamin K2 . J Cancer Res Clin Oncol 137, 779–787 (2011). https://doi.org/10.1007/s00432-010-0938-0

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  • DOI: https://doi.org/10.1007/s00432-010-0938-0

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