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Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain

  • Authors:
    • Lijia Pan
    • Litong Nie
    • Sheng Yao
    • Aiwei Bi
    • Yang Ye
    • Yeming Wu
    • Zhen Tan
    • Zhixiang Wu
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P.R. China, Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA, State Key Laboratory of Drug Research and Natural Products Chemistry Department, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P.R. China, State Key Laboratory of Drug Research and Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P.R. China
    Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2137-2149
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    Published online on: October 6, 2020
       https://doi.org/10.3892/ijmm.2020.4745
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Abstract

The prognosis of high‑risk neuroblastoma remains poor. Clinical first‑line drugs for treating neuroblastoma have been developed over the previous half‑century; however, progress in the identification of new drugs with high efficiency is required. Bufalin, one of the major components of extracts obtained from the venom of the Chinese toad Bufo gargarizans, which is used to treat heart failure in Asian Pacific countries, has been reported to be a potential drug against multiple types of tumor; however, the detailed mechanisms underlying its antitumor activities remain unclear, largely due to lack of knowledge regarding its targets. In the present study, bufalin was revealed to exhibit potent antitumor effects against neuroblastoma, both in vitro and in vivo, using cell proliferation, colony formation, Transwell migration and flow cytometry assays, as well as a nude mouse subcutaneous xenograft model. Moreover, a chemically modified bufalin probe was designed to identify the potential targets of bufalin in neuroblastoma via chemical proteomics. With this strategy, it was revealed that the electron transport chain (ETC) on the inner membrane of mitochondria may contain potential targets for bufalin, and that bufalin‑induced mitochondrial‑dependent apoptosis may be caused by disruption of the ETC. Collectively, the present study suggests that bufalin may a promising drug for chemotherapy against neuroblastoma, and provides a foundation for further studies into the antitumor mechanisms of bufalin.
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Copy and paste a formatted citation
Spandidos Publications style
Pan L, Nie L, Yao S, Bi A, Ye Y, Wu Y, Tan Z and Wu Z: Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain. Int J Mol Med 46: 2137-2149, 2020.
APA
Pan, L., Nie, L., Yao, S., Bi, A., Ye, Y., Wu, Y. ... Wu, Z. (2020). Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain. International Journal of Molecular Medicine, 46, 2137-2149. https://doi.org/10.3892/ijmm.2020.4745
MLA
Pan, L., Nie, L., Yao, S., Bi, A., Ye, Y., Wu, Y., Tan, Z., Wu, Z."Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain". International Journal of Molecular Medicine 46.6 (2020): 2137-2149.
Chicago
Pan, L., Nie, L., Yao, S., Bi, A., Ye, Y., Wu, Y., Tan, Z., Wu, Z."Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain". International Journal of Molecular Medicine 46, no. 6 (2020): 2137-2149. https://doi.org/10.3892/ijmm.2020.4745
Copy and paste a formatted citation
x
Spandidos Publications style
Pan L, Nie L, Yao S, Bi A, Ye Y, Wu Y, Tan Z and Wu Z: Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain. Int J Mol Med 46: 2137-2149, 2020.
APA
Pan, L., Nie, L., Yao, S., Bi, A., Ye, Y., Wu, Y. ... Wu, Z. (2020). Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain. International Journal of Molecular Medicine, 46, 2137-2149. https://doi.org/10.3892/ijmm.2020.4745
MLA
Pan, L., Nie, L., Yao, S., Bi, A., Ye, Y., Wu, Y., Tan, Z., Wu, Z."Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain". International Journal of Molecular Medicine 46.6 (2020): 2137-2149.
Chicago
Pan, L., Nie, L., Yao, S., Bi, A., Ye, Y., Wu, Y., Tan, Z., Wu, Z."Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain". International Journal of Molecular Medicine 46, no. 6 (2020): 2137-2149. https://doi.org/10.3892/ijmm.2020.4745
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