Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide
Joint Authors
Luo, Qihui
Huang, Chao
Liu, Wentao
Geng, Yi
Chen, Zhengli
Feng, Bin
Zou, Yuanfeng
Li, Lixia
Pang, Dejiang
Li, Chao
Yang, Chengcheng
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-19, 19 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-11-14
Country of Publication
Egypt
No. of Pages
19
Main Subjects
Abstract EN
The high recurrence frequency of gliomas but deficiency of effective treatment and prevalent chemoresistance have elicited interests in exploring and developing new agents.
Paris polyphyllins are monomers extracted from rhizome of Paris polyphylla var.
yunnanensis.
Here, we first reported that polyphyllin VII (PP7) exhibited cytotoxic effect on glioma cells.
PP7 significantly suppressed the viability and induced cell death of U87-MG and U251 cells after 24 h, with the IC50 values 4.24±0.87 μM and 2.17±0.14 μM, respectively.
Both apoptotic and autophagic processes were involved in the cytotoxic effect of PP7, as PP7 activated the Bcl2/Bax pathway and the inhibition of autophagy partly rescued the toxicity of PP7 in glioma cells.
In addition, an inhibition of AKT/mTORC1 activity was found after PP7 administration, and it seemed that the overproduction of reactive oxygen species (ROS) was responsible for this effect.
Namely, the removal of ROS by NAC treatment mitigated PP7-induced cell death, autophagy, and its effect on the AKT/mTORC1 signaling.
Additionally, a combination assay of PP7 with temozolomide (TMZ), the most used chemotherapy for glioma patients, was performed resulting in synergism, while PP7 reduced TMZ resistance through inhibition of MGMT expression.
Thus, our study reports PP7 as a potential agent for glioma treatment and reveals its underlying mechanisms of action.
American Psychological Association (APA)
Pang, Dejiang& Li, Chao& Yang, Chengcheng& Zou, Yuanfeng& Feng, Bin& Li, Lixia…[et al.]. 2019. Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-19.
https://search.emarefa.net/detail/BIM-1202375
Modern Language Association (MLA)
Pang, Dejiang…[et al.]. Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-19.
https://search.emarefa.net/detail/BIM-1202375
American Medical Association (AMA)
Pang, Dejiang& Li, Chao& Yang, Chengcheng& Zou, Yuanfeng& Feng, Bin& Li, Lixia…[et al.]. Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-19.
https://search.emarefa.net/detail/BIM-1202375
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202375