Polyphyllin VII induces apoptotic cell death via inhibition of the PI3K/Akt and NF‑κB pathways in A549 human lung cancer cells

He,Hao; Xu,Chang; Zheng,Lei; Wang,Kaidi; Jin,Manfei; Sun,Yanping; Yue,Zhenggang

doi:10.3892/mmr.2019.10879

Polyphyllin VII induces apoptotic cell death via inhibition of the PI3K/Akt and NF‑κB pathways in A549 human lung cancer cells

Authors:
- Hao He
- Chang Xu
- Lei Zheng
- Kaidi Wang
- Manfei Jin
- Yanping Sun
- Zhenggang Yue
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Affiliations: School of Pharmacy, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China, National Vaccine and Serum Institute, Beijing 100176, P.R. China, School of Public health, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, School of Pharmacy, Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China
Published online on: December 12, 2019 https://doi.org/10.3892/mmr.2019.10879
Pages: 597-606
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Polyphyllin VII is an active compound isolated from Paris polyphylla, which is termed Chonglou in China. The present study was designed to investigate the underlying mechanisms of the antitumor effect of Polyphyllin VII in lung cancer cells. The cytotoxic effect of Polyphyllin VII in human lung cancer A549 cells was analyzed; the results revealed an IC50 value of 0.41±0.10 µM at 24 h. The associated mechanisms were investigated by phase‑contrast microscopy, fluorescence microscopy, flow cytometry and western blot analysis. Exposure of A549 cells to Polyphyllin VII resulted in apoptosis. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF‑κB, and wortmannin, an inhibitor of PI3K, both decreased the proportion of viable A549 cells in the presence of Polyphyllin VII. The ratio of apoptotic cells increased in the presence of wortmannin and PDTC. Western blot analysis revealed that PI3K, phosphorylated (p)‑PI3K, Akt, p‑Akt, NF‑κB and p‑NF‑κB were downregulated following treatment with Polyphyllin VII. Increased caspase‑3 activity, increased poly‑(ADP‑ribose) polymerase cleavage and a downregulation of inhibitor of caspase‑activated DNase were observed following treatment with Polyphyllin VII, and these effects were enhanced by either wortmannin or PDTC. The present results revealed that Polyphyllin VII was able to induce apoptotic cell death in A549 human lung cancer cells via inhibition of the PI3K/Akt and NF‑κB pathways.

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