Open Access

Benzoyl‑xanthone derivative induces apoptosis in MCF‑7 cells by binding TRAF6

  • Authors:
    • Xuan Zhao
    • Limei Ren
    • Xiaoru Wang
    • Guangxin Han
    • Shuo Wang
    • Qingguo Yao
    • Yonghao Qi
  • View Affiliations

  • Published online on: December 30, 2021     https://doi.org/10.3892/etm.2021.11104
  • Article Number: 181
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

TNF receptor‑associated factor 6 (TRAF6) has been reported to be associated with the development of cancer. Nevertheless, the exact role of TRAF6 in cancer remains unclear. The purpose of the present study was to explore the mechanism of 2‑benzoyl‑3‑hydroxy‑4‑methyl‑9H‑xanthen‑9‑one leading to the inhibition of the activation of AKT and TGF‑β‑activated kinase 1 (TAK1), and to the apoptosis of MCF‑7 cells. Using a computational docking program and examination of AKT and TAK1 level changes, a new small molecule was identified, 2‑benzoyl‑3‑hydroxy‑4‑methyl‑9H‑xanthen‑9‑one, which competitively bound to TRAF6. Next, the effect of this new compound on MCF‑7 cells' biological behavior was studied in vitro. MTT assays were used to investigate cell viability; flow cytometry and invasion assays were performed to detect early apoptosis and invasion in MCF‑7 cells, respectively. Immunoprecipitation, western blotting and caspase‑3/9 activity assays were carried out to explore changes in protein expression. Briefly, the present data indicated that 2‑benzoyl‑3‑hydroxy‑4‑methyl‑9H‑xanthen‑9‑one could suppress proliferation, induce early apoptosis and inhibit invasion in MCF‑7 cells by suppressing the expression of Bcl‑2 and promoting the expression of Bax, caspase‑9, and caspase‑3. These findings indicated that 2‑benzoyl‑3‑hydroxy‑4‑methyl‑9H‑xanthen‑9‑one could induce apoptosis by inhibiting the activation of AKT and TAK1, and affecting the Bcl‑2/Bax‑caspase‑9‑caspase‑3 pathway by competitively binding with TRAF6.
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February-2022
Volume 23 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Zhao X, Ren L, Wang X, Han G, Wang S, Yao Q and Qi Y: Benzoyl‑xanthone derivative induces apoptosis in MCF‑7 cells by binding TRAF6. Exp Ther Med 23: 181, 2022.
APA
Zhao, X., Ren, L., Wang, X., Han, G., Wang, S., Yao, Q., & Qi, Y. (2022). Benzoyl‑xanthone derivative induces apoptosis in MCF‑7 cells by binding TRAF6. Experimental and Therapeutic Medicine, 23, 181. https://doi.org/10.3892/etm.2021.11104
MLA
Zhao, X., Ren, L., Wang, X., Han, G., Wang, S., Yao, Q., Qi, Y."Benzoyl‑xanthone derivative induces apoptosis in MCF‑7 cells by binding TRAF6". Experimental and Therapeutic Medicine 23.2 (2022): 181.
Chicago
Zhao, X., Ren, L., Wang, X., Han, G., Wang, S., Yao, Q., Qi, Y."Benzoyl‑xanthone derivative induces apoptosis in MCF‑7 cells by binding TRAF6". Experimental and Therapeutic Medicine 23, no. 2 (2022): 181. https://doi.org/10.3892/etm.2021.11104