Ruscogenin induces ferroptosis in pancreatic cancer cells

Song,Zhiwang; Xiang,Xiaojun; Li,Junhe; Deng,Jun; Fang,Ziling; Zhang,Ling; Xiong,Jianping

doi:10.3892/or.2019.7425

Ruscogenin induces ferroptosis in pancreatic cancer cells

Authors:
- Zhiwang Song
- Xiaojun Xiang
- Junhe Li
- Jun Deng
- Ziling Fang
- Ling Zhang
- Jianping Xiong
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Affiliations: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: December 10, 2019 https://doi.org/10.3892/or.2019.7425
Pages: 516-524
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic cancer is characterized by aggressive and highly metastatic phenotypes. This disease exhibits a poor patient prognosis and is considered a challenge due to the limited treatment options encountered in clinical practice. Previous studies have shown that ruscogenin, a saponin found in the root of Ophiopogon japonicus, exerts a wide range of biological functions including anticancer activity. In the present study, the effects of ruscogenin were investigated on pancreatic cancer cells and the potential molecular mechanism of this compound was explored. Cell viability was assessed using the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. Cell death was measured by trypan blue staining and by flow cytometry. The number of iron oxide nanoparticles was measured using Prussian blue staining. Reactive oxygen species (ROS) production was assessed using flow cytometry with dihydroethidium staining. Protein expression of the associated genes was assayed by western blotting. Furthermore, in vivo experiments were conducted to confirm the antitumor effects and assay the potential toxicity of ruscogenin in a nude mouse xenograft model. The results indicated that ruscogenin significantly repressed cell viability and induced cell death of pancreatic cancer cells in vitro in a dose‑ and time‑dependent manner. Furthermore, ruscogenin increased the concentration of intracellular ferrous irons and the production of ROS. This effect was inhibited by deferoxamine (DFO). Ruscogenin induced ferroptosis by regulating the levels of transferrin and ferroportin. These two proteins were involved in ruscogenin‑induced pancreatic cancer cell death. Finally, in vivo experiments demonstrated the antitumor effect of ruscogenin on pancreatic cancer xenografts in the absence of apparent toxicity. Taken collectively, the data demonstrated that ruscogenin exhibited anticancer effects in pancreatic cancer cells by inducing ferroptosis. The findings suggested that this compound may be further developed as a promising anticancer candidate for the treatment of pancreatic cancer.

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