Inhibition of tumor necrosis factor-α enhances apoptosis induced by nuclear factor-κB inhibition in leukemia cells

Dong,Qiao‑Mei; Ling,Chun; Chen,Xuan; Zhao,Li

doi:10.3892/ol.2015.3786

Inhibition of tumor necrosis factor-α enhances apoptosis induced by nuclear factor-κB inhibition in leukemia cells

Authors:
- Qiao‑Mei Dong
- Chun Ling
- Xuan Chen
- Li Zhao
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Affiliations: Central Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
Published online on: October 8, 2015 https://doi.org/10.3892/ol.2015.3786
Pages: 3793-3798

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Abstract

Inhibition of nuclear factor-κB (NF-κB) results in antitumor activity in leukemia cells, and may be a potential therapeutic strategy for the treatment of leukemia. However, a significant limitation of NF-κB inhibition in the treatment of leukemia is the low efficiency of this technique. NF‑κB inhibitor treatment induces apoptosis in leukemia cells; however, it additionally causes inflammatory molecules to induce increased sensitivity of healthy hematopoietic cells to cell death signals, therefore limiting its clinical applications. Tumor necrosis factor‑α (TNF‑α) is a key regulator of inflammation, and induces a variety of actions in leukemic and healthy hematopoietic cells. TNF‑α induces NF‑κB‑dependent and ‑independent survival signals, promoting the proliferation of leukemia cells. However, in healthy hematopoietic cells, TNF‑α induces death signaling, an effect which is enhanced by the inhibition of NF‑κB. Based on these observations, the present study hypothesized that inhibition of TNF‑α signaling may be able to protect healthy hematopoietic cells and other tissue cells, while increasing the anti‑leukemia effects of NF‑κB inhibition on leukemia cells. The role and underlying molecular mechanisms of TNF‑α inhibition in the regulation of NF‑κB inhibition‑induced apoptosis in leukemia cells was therefore investigated in the present study. The results indicated that inhibition of TNF‑α enhanced NF‑κB inhibition‑induced apoptosis in leukemia cells. It was also revealed that protein kinase B was significant in the regulation of TNF-α and NF-κB inhibition-induced apoptosis. During this process, intrinsic apoptotic pathways were activated. A combination of NF-κB and TNF-α inhibition may be a potential specific and effective novel therapeutic strategy for the treatment of leukemia.

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