Polyphyllin VII induces apoptosis and autophagy via mediating H2O2 levels and the JNK pathway in human osteosarcoma U2OS cells

Li,Xiangde; Liu,Yun; Liao,Shijie; Lin,Chengsen; Moro,Abu; Liu,Jing; Feng,Wenyu; Wang,Kun; Wang,Chunming

doi:10.3892/or.2020.7866

Polyphyllin VII induces apoptosis and autophagy via mediating H2O2 levels and the JNK pathway in human osteosarcoma U2OS cells

Authors:
- Xiangde Li
- Yun Liu
- Shijie Liao
- Chengsen Lin
- Abu Moro
- Jing Liu
- Wenyu Feng
- Kun Wang
- Chunming Wang
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Affiliations: Department of Radiation Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530007, P.R. China, Department of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Intervention, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530021, P.R. China
Published online on: November 23, 2020 https://doi.org/10.3892/or.2020.7866
Pages: 180-190
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Polyphyllin VII, a compound extracted from the rhizomes of Paris polyphylla, has strong antitumor effects on various human tumor cell lines. However, few studies have reported the possible effect of Polyphyllin VII on human osteosarcoma (OS) cell lines. The present study revealed that Polyphyllin VII promoted OS cell apoptosis and inhibited cell proliferation via upregulating the expression of LC3II, Atg5, Atg7 and the Atg12‑Atg5 complex. By contrast, treatment of OS cells with Polyphyllin VII downregulated Atg12 and p62 expression. Following treatment with class III PI 3‑kinase inhibitor (3‑MA; an autophagy inhibitor), the Polyphyllin VII‑mediated apoptotic effect was reversed. These findings indicated that the inhibition of autophagy could attenuate U2OS cell apoptosis in cells treated with high concentrations of Polyphyllin VII. The present study also demonstrated that Polyphyllin VII upregulated the intracellular hydrogen peroxide (H2O2) levels in U2OS cells. However, treatment of U2OS cells with N‑acetyl‑L cysteine (NAC) effectively reversed this effect. The western blot analysis results indicated that the c‑Jun N‑terminal kinase (JNK) signaling pathway was closely associated with Polyphyllin VII‑induced apoptosis and autophagy. In conclusion, the results of the present study demonstrated that Polyphyllin VII could effectively inhibit cell viability and promote autophagy and apoptosis in U2OS cells. In addition, the mechanism underlying these effects could be associated with the intracellular H2O2 levels and the JNK signaling pathway.

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