TY - JOUR
T1 - Bufalin exerts antitumor effects in neuroblastoma via the induction of reactive oxygen species‑mediated apoptosis by targeting the electron transport chain
AU - Pan, Lijia
AU - Nie, Litong
AU - Yao, Sheng
AU - Bi, Aiwei
AU - Ye, Yang
AU - Wu, Yeming
AU - Tan, Zhen
AU - Wu, Zhixiang
N1 - Publisher Copyright:
© 2020 Spandidos Publications. All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Bufalin
KW - Chemical proteomics
KW - ETc
KW - Mitochondria
KW - Neuroblastoma
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U2 - 10.3892/ijmm.2020.4745
DO - 10.3892/ijmm.2020.4745
M3 - Article
C2 - 33125107
AN - SCOPUS:85094663611
SN - 1107-3756
VL - 46
SP - 2137
EP - 2149
JO - International journal of molecular medicine
JF - International journal of molecular medicine
IS - 6
ER -