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Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma

  • Authors:
    • Jiabin Zhu
    • Jun Zhao
    • Zhenlong Yu
    • Sandeep Shrestha
    • Jing Song
    • Wenwen Liu
    • Wen Lan
    • Jinshan Xing
    • Shuang Liu
    • Chen Chen
    • Momo Cao
    • Xiuzhen Sun
    • Qi Wang
    • Xishuang Song
  • View Affiliations / Copyright

    Affiliations: Department of Urology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Neurosurgery, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Department of Respiratory Medicine, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116023, P.R. China, Department of Neurosurgery, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116023, P.R. China, Department of Gastroenterology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116023, P.R. China, Department of Cardiovascular Medicine, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Hepatobiliary Surgery, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Otorhinolaryngology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116023, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 987-1000
    |
    Published online on: June 29, 2018
       https://doi.org/10.3892/ijo.2018.4460
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Abstract

Parthenolide (PTL) is a sesquiterpene lactone compound obtained from Tanacetum parthenium (feverfew) and inhibits the activation of nuclear factor (NF)-κB. Epoxymicheliolide (EMCL) is a compound which is structurally related to PTL; however, EMCL is more stable under acidic and alkaline conditions. As a biologically active molecule, the detailed mechanism by which EMCL inhibits tumor activity remains to be elucidated. The present study evaluated the effect of EMCL on renal cell carcinoma (RCC) cells and identified the underlying mechanisms. It was found that treatment with EMCL significantly inhibited the proliferation of RCC cells in vitro and increased the induction of apoptosis by activating the mitochondria- and caspase-dependent pathway. Simultaneously, EMCL suppressed cell invasion and metastasis by inhibiting epithelial-mesenchymal transition, as observed in a microfluidic chip assay. Furthermore, using immunofluorescence analysis, an electrophoretic mobility shift assay and a dual-luciferase reporter assay, it was shown that treatment with EMCL significantly suppressed the expression of cyclooxygenase‑2 by inhibiting the translocation of NF‑κB p50/p65 and the activity of NF‑κB. Collectively, the results indicated that EMCL suppressed tumor growth by inhibiting the activation of NF‑κB and suggested that EMCL may be a novel anticancer agent in the treatment of RCC.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu J, Zhao J, Yu Z, Shrestha S, Song J, Liu W, Lan W, Xing J, Liu S, Chen C, Chen C, et al: Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma. Int J Oncol 53: 987-1000, 2018.
APA
Zhu, J., Zhao, J., Yu, Z., Shrestha, S., Song, J., Liu, W. ... Song, X. (2018). Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma. International Journal of Oncology, 53, 987-1000. https://doi.org/10.3892/ijo.2018.4460
MLA
Zhu, J., Zhao, J., Yu, Z., Shrestha, S., Song, J., Liu, W., Lan, W., Xing, J., Liu, S., Chen, C., Cao, M., Sun, X., Wang, Q., Song, X."Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma". International Journal of Oncology 53.3 (2018): 987-1000.
Chicago
Zhu, J., Zhao, J., Yu, Z., Shrestha, S., Song, J., Liu, W., Lan, W., Xing, J., Liu, S., Chen, C., Cao, M., Sun, X., Wang, Q., Song, X."Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma". International Journal of Oncology 53, no. 3 (2018): 987-1000. https://doi.org/10.3892/ijo.2018.4460
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu J, Zhao J, Yu Z, Shrestha S, Song J, Liu W, Lan W, Xing J, Liu S, Chen C, Chen C, et al: Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma. Int J Oncol 53: 987-1000, 2018.
APA
Zhu, J., Zhao, J., Yu, Z., Shrestha, S., Song, J., Liu, W. ... Song, X. (2018). Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma. International Journal of Oncology, 53, 987-1000. https://doi.org/10.3892/ijo.2018.4460
MLA
Zhu, J., Zhao, J., Yu, Z., Shrestha, S., Song, J., Liu, W., Lan, W., Xing, J., Liu, S., Chen, C., Cao, M., Sun, X., Wang, Q., Song, X."Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma". International Journal of Oncology 53.3 (2018): 987-1000.
Chicago
Zhu, J., Zhao, J., Yu, Z., Shrestha, S., Song, J., Liu, W., Lan, W., Xing, J., Liu, S., Chen, C., Cao, M., Sun, X., Wang, Q., Song, X."Epoxymicheliolide, a novelguaiane-type sesquiterpene lactone, inhibits NF‑κB/COX‑2 signaling pathways by targeting leucine 281 and leucine 25 in IKKβ in renal cell carcinoma". International Journal of Oncology 53, no. 3 (2018): 987-1000. https://doi.org/10.3892/ijo.2018.4460
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