Mechanisms of Dihydroartemisinin and Dihydroartemisinin/Holotransferrin Cytotoxicity in T-Cell Lymphoma Cells

PLoS One. 2015 Oct 26;10(10):e0137331. doi: 10.1371/journal.pone.0137331. eCollection 2015.

Abstract

The validated therapeutic effects of dihydroartemisinin (DHA) in solid tumors have encouraged us to explore its potential in treating T-cell lymphoma. We found that Jurkat cells (a T-cell lyphoma cell line) were sensitive to DHA treatment with a IC50 of dihydroartemisinin. The cytotoxic effect of DHA in Jurkat cells showed a dose- and time- dependent manner. Interestingly, the cytotoxic effect of DHA was further enhanced by holotransferrin (HTF) due to the high expression of transferrin receptors in T-cell lymphoma. Mechanistically, DHA significantly increased the production of intracellular reactive oxygen species, which led to cell cycle arrest and apoptosis. The DHA treatment also inhibited the expression of protumorgenic factors including VEGF and telomerase catalytic subunit. Our results have proved the therapeutic effect of DHA in T-cell lymphoma. Especially in combination with HTF, DHA may provide a novel efficient approach in combating the deadly disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / toxicity*
  • Apoptosis / drug effects
  • Artemisinins / toxicity*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Gene Expression
  • Humans
  • Jurkat Cells
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / metabolism*
  • RNA, Messenger / genetics
  • Reactive Oxygen Species / metabolism
  • Receptors, Transferrin / genetics
  • Telomerase / metabolism
  • Transferrin / toxicity*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Antineoplastic Agents
  • Artemisinins
  • RNA, Messenger
  • Reactive Oxygen Species
  • Receptors, Transferrin
  • Transferrin
  • Vascular Endothelial Growth Factor A
  • holotransferrin
  • dihydroartemisinin
  • Telomerase

Grant support

This work was supported by the Science & Technology Development Program of Shandong Province, China (2012GSF11819).