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Article

Levistolide A synergistically enhances doxorubicin‑induced apoptosis of k562/dox cells by decreasing MDR1 expression through the ubiquitin pathway

  • Authors:
    • Yuanyuan Ding
    • Weibo Niu
    • Tao Zhang
    • Jue Wang
    • Jiao Cao
    • He Chen
    • Ruiqi Wang
    • Hongli An
  • View Affiliations / Copyright

    Affiliations: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Institute of Materia Medica, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
  • Pages: 1198-1208
    |
    Published online on: November 27, 2018
       https://doi.org/10.3892/or.2018.6889
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Abstract

Multidrug resistance (MDR) is one of the main reasons underlying failure of cancer chemotherapy. Certain natural compounds may help prevent MDR, and may be used in combination with chemotherapeutic agents to enhance their efficacy. Levistolide A is a natural product that is extracted from the rhizome of Angelicae sinensis (Oliv.), which has been used as an essential component of antitumor formulas since ancient times in China. The present study conducted the following experiments: MTT assay, apoptosis analysis, cellular doxorubicin accumulation assay, immunoblotting and reverse transcription‑quantitative polymerase chain reaction, to investigate whether levistolide A enhance doxorubicin‑induced apoptosis of k562/dox cells and to determine the molecular mechanisms involved. When combined with doxorubicin, levistolide A exhibited a synergistic effect and induced cytotoxicity in k562/dox cells. Drug accumulation studies revealed that levistolide A increased the intracellular concentration of doxorubicin in a dose‑dependent manner. Cell apoptosis experiments indicated that levistolide A increased the sensitivity of k562/dox cells to doxorubicin. Furthermore, detection of reactive oxygen species (ROS) revealed that levistolide A enhanced doxorubicin‑induced cell death by increasing the levels of ROS. Mitochondrial potential detection with JC‑1 staining also indicated that levistolide A synergistically enhanced doxorubicin‑induced cell death. Immunoblotting demonstrated that levistolide A enhanced doxorubicin‑induced cell death by decreasing the expression levels of B‑cell lymphoma 2 and increasing caspase 3 expression. Furthermore, multidrug resistance protein 1 (MDR1) expression in k562/dox cells was downregulated by levistolide A in a dose‑dependent manner, thus suggesting that levistolide A may modulate MDR1 during cancer therapy. Therefore, the combination of levistolide A with doxorubicin could result in more effective and less toxic anticancer regimens.
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Copy and paste a formatted citation
Spandidos Publications style
Ding Y, Niu W, Zhang T, Wang J, Cao J, Chen H, Wang R and An H: Levistolide A synergistically enhances doxorubicin‑induced apoptosis of k562/dox cells by decreasing MDR1 expression through the ubiquitin pathway. Oncol Rep 41: 1198-1208, 2019.
APA
Ding, Y., Niu, W., Zhang, T., Wang, J., Cao, J., Chen, H. ... An, H. (2019). Levistolide A synergistically enhances doxorubicin‑induced apoptosis of k562/dox cells by decreasing MDR1 expression through the ubiquitin pathway. Oncology Reports, 41, 1198-1208. https://doi.org/10.3892/or.2018.6889
MLA
Ding, Y., Niu, W., Zhang, T., Wang, J., Cao, J., Chen, H., Wang, R., An, H."Levistolide A synergistically enhances doxorubicin‑induced apoptosis of k562/dox cells by decreasing MDR1 expression through the ubiquitin pathway". Oncology Reports 41.2 (2019): 1198-1208.
Chicago
Ding, Y., Niu, W., Zhang, T., Wang, J., Cao, J., Chen, H., Wang, R., An, H."Levistolide A synergistically enhances doxorubicin‑induced apoptosis of k562/dox cells by decreasing MDR1 expression through the ubiquitin pathway". Oncology Reports 41, no. 2 (2019): 1198-1208. https://doi.org/10.3892/or.2018.6889
Copy and paste a formatted citation
x
Spandidos Publications style
Ding Y, Niu W, Zhang T, Wang J, Cao J, Chen H, Wang R and An H: Levistolide A synergistically enhances doxorubicin‑induced apoptosis of k562/dox cells by decreasing MDR1 expression through the ubiquitin pathway. Oncol Rep 41: 1198-1208, 2019.
APA
Ding, Y., Niu, W., Zhang, T., Wang, J., Cao, J., Chen, H. ... An, H. (2019). Levistolide A synergistically enhances doxorubicin‑induced apoptosis of k562/dox cells by decreasing MDR1 expression through the ubiquitin pathway. Oncology Reports, 41, 1198-1208. https://doi.org/10.3892/or.2018.6889
MLA
Ding, Y., Niu, W., Zhang, T., Wang, J., Cao, J., Chen, H., Wang, R., An, H."Levistolide A synergistically enhances doxorubicin‑induced apoptosis of k562/dox cells by decreasing MDR1 expression through the ubiquitin pathway". Oncology Reports 41.2 (2019): 1198-1208.
Chicago
Ding, Y., Niu, W., Zhang, T., Wang, J., Cao, J., Chen, H., Wang, R., An, H."Levistolide A synergistically enhances doxorubicin‑induced apoptosis of k562/dox cells by decreasing MDR1 expression through the ubiquitin pathway". Oncology Reports 41, no. 2 (2019): 1198-1208. https://doi.org/10.3892/or.2018.6889
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