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Ionomycin inhibits Jurkat T cell behaviors in the presence of phorbol-12,13-dibutyrate

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Abstract

Ionomycin in conjunction with phorbol-12,13-dibutyrate (PDBu) is conventionally used as a stimulator to activate cells, especially original T cells. But we accidently found it had an entirely opposite action on malignant tumor cells derived from T cells. Thus, influence of ionomycin on human leukemia Jurkat T cell behaviors and its preliminary mechanistic process were explored in the presence of PDBu. Ionomycin could remarkably inhibit colony formation of the cells, and inhibitory rate of the cell proliferation was increased with ionomycin treatment in a dose- or time-related relationship, following the reduction of ERK1/2 and phosphorylated-ERK1/2 levels. However, a high dose of ionomycin might moderately repress mid-stage activation of the cells. It also blocked the cell entry at S-phase and G2/M-phase with the attenuation of transforming growth factor-β (TGF-β) level in the cells, and promoted the cell apoptosis following the augment of caspase-3 and cleaved caspase-3 in the cells. The dramatic elevation of [Ca2+]i and intracellular pH (pHi) was simultaneously followed by the above alteration of the cell behaviors. These results indicate that ionomycin may strongly inhibit human acute T lymphocyte leukemia progress in the presence of PDBu through the inhibition of ERK1/2 signaling, the activation of caspase-3 and the attenuation of TGF-β mediated by the [Ca2+]i and pHi enhancement, providing a novel insight into function and potential application of both ionomycin and PDBu.

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Acknowledgments

This work was supported by the National Natural Science Foundations of China (No 81172824, No 30971465, No 30471635).

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou, 510632, China

    Yuan Wang, Wenting Hao, Jingfang Di, Shan Zeng, Jing Liu & Feiyue Xing

  2. Life Sciences and Technology Base of Basic Science Grade 2011, Lanzhou University School of Life Sciences, Lanzhou, 730000, China

    Rui Xing

  3. Department of Stomatology, Jinan University, Guangzhou, 510632, China

    Jing Liu

  4. Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University, Guangzhou, 510632, China

    Feiyue Xing

Authors
  1. Yuan Wang
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  2. Wenting Hao
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  3. Rui Xing
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  4. Jingfang Di
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  5. Shan Zeng
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  6. Jing Liu
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  7. Feiyue Xing
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Correspondence to Jing Liu or Feiyue Xing.

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Wang, Y., Hao, W., Xing, R. et al. Ionomycin inhibits Jurkat T cell behaviors in the presence of phorbol-12,13-dibutyrate. Ann Hematol 93, 735–746 (2014). https://doi.org/10.1007/s00277-013-1955-2

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  • DOI: https://doi.org/10.1007/s00277-013-1955-2

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