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

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.

• Authors: Yuan Wang, Wenting Hao, Rui Xing, Jingfang Di, Shan Zeng, Jing Liu, Feiyue Xing
• Journal: Annals of hematology (Ann Hematol) Vol. 93 Issue 5 Pg. 735-46 (May 2014) ISSN: 1432-0584 [Electronic] Germany
• PMID: 24292536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Ionophores
• Drug Combinations
• Transforming Growth Factor beta
• Phorbol 12,13-Dibutyrate
• Ionomycin
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Caspase 3
• Calcium

Topics

• Apoptosis (drug effects)
• Calcium (metabolism)
• Calcium Ionophores (pharmacology)
• Caspase 3 (genetics, metabolism)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Combinations
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Gene Expression Regulation, Leukemic (drug effects)
• Humans
• Hydrogen-Ion Concentration
• Ionomycin (pharmacology)
• Jurkat Cells
• Lymphocyte Activation (drug effects)
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Phorbol 12,13-Dibutyrate (pharmacology)
• S Phase (drug effects)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta (genetics, metabolism)