Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide
Identifieur interne : 000527 ( Main/Merge ); précédent : 000526; suivant : 000528Polyphyllin VII Promotes Apoptosis and Autophagic Cell Death via ROS-Inhibited AKT Activity, and Sensitizes Glioma Cells to Temozolomide
Auteurs : Dejiang Pang [République populaire de Chine] ; Chao Li [République populaire de Chine] ; Chengcheng Yang [République populaire de Chine] ; Yuanfeng Zou [République populaire de Chine] ; Bin Feng [République populaire de Chine] ; Lixia Li [République populaire de Chine] ; Wentao Liu [République populaire de Chine] ; Yi Geng [République populaire de Chine] ; Qihui Luo [République populaire de Chine] ; Zhengli Chen [République populaire de Chine] ; Chao Huang [République populaire de Chine]Source :
- Oxidative Medicine and Cellular Longevity [ 1942-0900 ] ; 2019.
Abstract
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
Url:
DOI: 10.1155/2019/1805635
PubMed: 31814867
PubMed Central: 6877958
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PMC:6877958Le document en format XML
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<author><name sortKey="Pang, Dejiang" sort="Pang, Dejiang" uniqKey="Pang D" first="Dejiang" last="Pang">Dejiang Pang</name>
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<author><name sortKey="Yang, Chengcheng" sort="Yang, Chengcheng" uniqKey="Yang C" first="Chengcheng" last="Yang">Chengcheng Yang</name>
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<author><name sortKey="Chen, Zhengli" sort="Chen, Zhengli" uniqKey="Chen Z" first="Zhengli" last="Chen">Zhengli Chen</name>
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<author><name sortKey="Huang, Chao" sort="Huang, Chao" uniqKey="Huang C" first="Chao" last="Huang">Chao Huang</name>
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<affiliation wicri:level="1"><nlm:aff id="I3">Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130</wicri:regionArea>
<wicri:noRegion>Chengdu 611130</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Oxidative Medicine and Cellular Longevity</title>
<idno type="ISSN">1942-0900</idno>
<idno type="eISSN">1942-0994</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
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<profileDesc><textClass></textClass>
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<front><div type="abstract" xml:lang="en"><p>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 <italic>μ</italic>
M and 2.17 ± 0.14 <italic>μ</italic>
M, 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.</p>
</div>
</front>
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<author><name sortKey="Jiang, S X" uniqKey="Jiang S">S. X. Jiang</name>
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<author><name sortKey="Reardon, D A" uniqKey="Reardon D">D. A. Reardon</name>
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<author><name sortKey="Caporaso, P" uniqKey="Caporaso P">P. Caporaso</name>
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<author><name sortKey="Bonmassar, L" uniqKey="Bonmassar L">L. Bonmassar</name>
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<biblStruct><analytic><author><name sortKey="Zhang, L H" uniqKey="Zhang L">L.-H. Zhang</name>
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<author><name sortKey="Yin, A A" uniqKey="Yin A">A.-A. Yin</name>
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<author><name sortKey="Cheng, J X" uniqKey="Cheng J">J.-X. Cheng</name>
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