Journal of Functional Foods (Apr 2023)

3-Hydroxymorindone from Knoxia roxburghii (Spreng.) M. A. Rau induces ROS-mediated mitochondrial dysfunction cervical cancer cells apoptosis via inhibition of PI3K/AKT/NF-κB signaling pathway

  • Xiao-Jiao Chen,
  • Zhi-Bo Liu,
  • Xue Li,
  • Xue-Mei Pu,
  • Mi-Jia Mei,
  • Xin-Ying Pu,
  • Xin-Ge Wang,
  • Jun-Jie Hao,
  • Fan Zhang,
  • Bin Qiu,
  • Jie Yu

Journal volume & issue
Vol. 103
p. 105498

Abstract

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Knoxia roxburghii (Spreng.) M. A. Rau (KR) is used in Chinese traditional medicine with potential anti-cancer effects. Previous studies have shown that anthraquinone component 3-hydroxymorindone (3-H) isolated from KR has a strong cytotoxic effect on tumor cells, but its molecular mechanism has not been studied yet. The cytotoxicity of 3-H to different tumor cells has been demonstrated in the present study. Network pharmacology and molecular biology techniques were used to explore the possible mechanism of cervical cancer cells (HeLa, SiHa, and C33A cells) with the most significant toxicity. 3-H inhibited the proliferation and migration of cervical cancer cells, triggered ROS accumulation, reduced mitochondrial membrane potential (ΔΨM), and cell apoptosis. Western blotting analysis showed that it could induce HeLa cells apoptosis by down-regulating the PI3K/AKT/NF-κB signaling pathway. Moreover, ROS inhibitor inhibited 3-H-induced cell proliferation and PI3K inhibitor synergized 3-H-induced cell proliferation inhibition. As well as, the inhibition of p-PI3K, p-Akt, and p-NF-κB by 3-H could be compensated by the ROS inhibitor. Taken together, these results suggest that 3-H induces apoptosis of human cervical cancer cells by up-regulating ROS-mediated mitochondrial dysfunction and down-regulating PI3K/AKT/NF-κB signaling pathways. The result of this research provides a promising potential compound for the development of anti-cervical cancer drugs.

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