Tumor Biology

, Volume 37, Issue 1, pp 531–539 | Cite as

Synergistic action of 5Z-7-oxozeaenol and bortezomib in inducing apoptosis of Burkitt lymphoma cell line Daudi

  • Jie Zhang
  • Bing Li
  • Haixia Wu
  • Jiayao Ou
  • Rongbin Wei
  • Junjun Liu
  • Wenping Cai
  • Xiaodong Liu
  • Shouliang Zhao
  • Jianhua Yang
  • Lili Zhou
  • Shangfeng Liu
  • Aibin Liang
Original Article


Treatment failure in cancer chemotherapy is largely due to the toxic effects of chemotherapeutic agents on normal cells/tissues. The proteasome inhibitor bortezomib has been successfully applied to treat multiple myeloma (MM), but there are some common adverse reactions in the clinic including peripheral neuropathy (PN). The TAK1 selective inhibitor 5Z-7-oxozeaenol has been widely studied in cancer therapy. Here, we investigated the potential synergy of bortezomib and 5Z-7-oxozeaenol in Burkitt’s lymphoma (BL) cell lines. Cell viability assay showed that co-treatment of bortezomib at 8 nM, representing a one-eighth concentration for growth arrest, and 5Z-7-oxozeaenol at 2 μM, a dose that exhibited insignificant cytotoxic effects, synergistically induced apoptosis in the cell line Daudi. In parallel with the increasing dose of the bortezomib, and 5Z-7-oxozeaenol at 0.5 μM, lower colony formation efficiencies were seen in the cell line Daudi. Western blotting analysis verified that TAK1 inhibition by 5Z-7-oxozeaenol completely blocked JNK, p38, Erk, IKK, and IκB phosphorylation, which was almost instantly activated by TAK1 both directly or indirectly. Both agents synergistically prevented nuclear translocation of NF-κB, a characteristic of NF-κB inactivation. Moreover, a synergistic effect of bortezomib and 5Z-7-oxozeaenol on Western blotting analysis and flow cytometry was disclosed. Collectively, our results indicated that the proteasome inhibitor bortezomib and the TAK1 inhibitor 5Z-7-oxozeaenol displayed synergy on inhibiting BL cell apoptosis by inhibiting NF-κB activity.


NF-κB Bortezomib 5Z-7-oxozeaenol TAK1 Burkitt’s lymphoma 



This work was supported by the National Natural Science Foundation of China (81270615), and the Outstanding Discipline Leaders of Shanghai Health System Support Program (XBR2013077).

Conflicts of interest

No conflict of interest exits in the submission of this manuscript, and the manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part.

Author contributions

J. Z. and B. L.: manuscript writing and editing; H. W., J. O., R. W., J. L., W. C., X. L., S. Z., J. Y., and L. Z.: critical discussion for conception and design; S. L. and A. L.: conception and design, manuscript writing and editing, and final approval of manuscript.

Supplementary material

13277_2015_3832_MOESM1_ESM.pptx (101 kb)
Fig. S1 5Z-7-oxozeaenol enhances the cytotoxic effect of bortezomib on Burkitt lymphoma cell Daudi. Daudi cells were seeded into 96-well plates at a concentration of 1.5 × 104/well. After 16 h, cells were incubated with drugs combinational or respective for 24/48/72/96 h at indicated concentrations and cell viability was assessed by CCK-8 assay. Results presented as % vehicle ± SD (n = 5). ***P ≤ 0.001, **P ≤ 0.01, *P ≤ 0.05 (Student’s t test, two-tailed) (PPTX 100 kb)
13277_2015_3832_MOESM2_ESM.pptx (78 kb)
Fig. S2 Cytotoxic effect of 5Z-7-oxozeaenol and bortezomib on Burkitt lymphoma cells Raji or NAMALWA. Raji or NAMALWA cells were seeded in 96-well plates at a concentration of 1.5 × 104 cells per well. After 16 h, cells were incubated with drugs for 24 h at indicated concentrations, and growth inhibition was assessed by CCK-8 assay. Results presented as % vehicle ± SD (n = 5). P > 0.05 (Student’s t test, two-tailed) (PPTX 78 kb)
13277_2015_3832_MOESM3_ESM.pptx (88 kb)
Fig. S3 5Z-7-oxozeaenol inhibits Erk, p38 activation in Daudi. Daudi cells were treated with bortezomib at the indicated time points (0, 2, 5, 10, 15 min) with or without 5Z-7-oxozeaenol, total protein extracts were subjected to SDS-PAGE and immunoblotted with antibodies indicated. β-tubulin was detected as a loading control for whole cell extracts (PPTX 87 kb)
13277_2015_3832_MOESM4_ESM.pptx (234 kb)
Fig. S4 BaF-3 cells were treated with bortezomib (8 nM) and 5Z-7-oxozeaenol (2 μM) for 24/48 h and examined by flow cytometry using Annexin-V/PI staining to label apoptotic cells (PPTX 233 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jie Zhang
    • 1
    • 2
    • 3
  • Bing Li
    • 1
  • Haixia Wu
    • 1
  • Jiayao Ou
    • 4
  • Rongbin Wei
    • 4
  • Junjun Liu
    • 4
  • Wenping Cai
    • 4
  • Xiaodong Liu
    • 5
  • Shouliang Zhao
    • 3
  • Jianhua Yang
    • 4
  • Lili Zhou
    • 1
  • Shangfeng Liu
    • 3
  • Aibin Liang
    • 1
  1. 1.Department of HematologyTongji Hospital, Tongji University School of MedicineShanghaiChina
  2. 2.College of life sciencesGuizhou UniversityGuiyangChina
  3. 3.Department of StomatologyHuashan Hospital, Fudan UniversityShanghaiChina
  4. 4.Department of OphthalmologyShanghai Tenth People’s Hospital, Tongji University School of MedicineShanghaiChina
  5. 5.Department of NeurosurgeryHuashan Hospital, Fudan UniversityShanghaiChina

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