OncoTargets and Therapy (Mar 2020)

Polyphyllin VI Induces Apoptosis and Autophagy via Reactive Oxygen Species Mediated JNK and P38 Activation in Glioma

  • Liu W,
  • Chai Y,
  • Hu L,
  • Wang J,
  • Pan X,
  • Yuan H,
  • Zhao Z,
  • Song Y,
  • Zhang Y

Journal volume & issue
Vol. Volume 13
pp. 2275 – 2288

Abstract

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Wei Liu,1 Yi Chai,1 Libo Hu,1 Junhua Wang,2 Xin Pan,2 Hongyu Yuan,3 Zitong Zhao,3 Yongmei Song,3 Yuqi Zhang1 1School of Clinical Medicine, Tsinghua University, Beijing 10084, People’s Republic of China; 2Department of Neurosurgery, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing 100040, People’s Republic of China; 3State Key Laboratory of Molecular Oncology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of ChinaCorrespondence: Yuqi ZhangSchool of Clinical Medicine, Tsinghua University, No. 1, Tsinghua Yuan, Haidian District, Beijing 10084, People’s Republic of ChinaEmail [email protected] SongState Key Laboratory of Molecular Oncology,National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuannanli, Chaoyang, Beijing 100021, People’s Republic of ChinaEmail [email protected]: Polyphyllin VI (PPVI), a bioactive component derived from a traditional Chinese herb Paris polyphylla, exhibits potential antitumor activity against hepatocellular carcinoma, as well as breast and lung cancers. However, its effect on glioma remains unknown.Methods: Five glioma cell lines (U251, U343, LN229, U87 and HEB) and an animal model were employed in the study. Anti-proliferation effects of PPVI were first determined using CCK-8 cell proliferation and clone formation assays, then reactive oxygen species (ROS), cell cycle progression and apoptosis effects measured by flow cytometry. The effect of PPVI on protein expression was quantified by Western blot analysis.Results: Data showed that PPVI inhibited the proliferation of glioma cell lines by modulating the G2/M phase. Additionally, incubation of cells with PPVI promoted apoptosis, autophagy, increased accumulation of ROS and activated ROS-modulated JNK and p38 pathways. On the other hand, N-acetyl cysteine, a ROS inhibitor, attenuated PPVI-triggered effects. Furthermore, JNK and p38 inhibitors ameliorated PPVI-triggered autophagy and apoptosis in glioma cells. In vivo assays showed that PPVI inhibited tumor growth of U87 cell line in nude mice.Conclusion: Overall, these data suggested that PPVI might be an effective therapeutic agent for glioma.Keywords: polyphyllin VI, glioma, autophagy, apoptosis, reactive oxygen species

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