Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells
Abstract Glioma is the most general primary and lethal intracranial malignant tumor. Pterostilbene (PTE), an analog of stilbene and resveratrol, has attracted attention in recent years due to its significant antitumor activity in multiple solid tumors; however, its effect on drug-resistant glioma ce...
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oai:doaj.org-article:eaae9165681e4b31bc97d6246ae0504d2021-12-02T13:17:42ZPterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells10.1038/s41598-021-85908-w2045-2322https://doaj.org/article/eaae9165681e4b31bc97d6246ae0504d2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85908-whttps://doaj.org/toc/2045-2322Abstract Glioma is the most general primary and lethal intracranial malignant tumor. Pterostilbene (PTE), an analog of stilbene and resveratrol, has attracted attention in recent years due to its significant antitumor activity in multiple solid tumors; however, its effect on drug-resistant glioma cells and the underlying mechanism have not yet been reported. In this study, we found that pterostilbene inhibited proliferation, induced intrinsic mitochondria-mediated apoptosis and caused S phase arrest, inhibited migration and excessive invasion in glioma cells. Pretreatment with the pan-caspase-inhibitor Z-VAD-FMK attenuated the PTE-induced apoptosis of glioma cells. Moreover, PTE significantly increased the production of reactive oxygen species (ROS) and reduce the mitochondrial membrane potential (MMP). Inhibition of ROS with N-acetyl-l-cysteine not only rescued PTE-induced reduction of cellular viability but also prevented glioma cell apoptosis. We also discovered ERK 1/2 and JNK signaling pathways were activated by PTE and contributed to induce glioma cell apoptosis. In addition, specific inhibitors of ERK 1/2 and JNK attenuated PTE-induced apoptosis. Besides, PTE significantly reduced tumor volume and prolonged median survival of tumor-bearing rats in vivo. In summary, the results of this study indicate that the anti-tumor effect of PTE on glioma cells may provide a new treatment option for glioma patients.Haijun GaoZiqiang LiuWeidong XuQunhui WangChaochao ZhangYaonan DingWeiguang NieJiacheng LaiYong ChenHaiyan HuangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021) |
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Medicine R Science Q Haijun Gao Ziqiang Liu Weidong Xu Qunhui Wang Chaochao Zhang Yaonan Ding Weiguang Nie Jiacheng Lai Yong Chen Haiyan Huang Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells |
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Abstract Glioma is the most general primary and lethal intracranial malignant tumor. Pterostilbene (PTE), an analog of stilbene and resveratrol, has attracted attention in recent years due to its significant antitumor activity in multiple solid tumors; however, its effect on drug-resistant glioma cells and the underlying mechanism have not yet been reported. In this study, we found that pterostilbene inhibited proliferation, induced intrinsic mitochondria-mediated apoptosis and caused S phase arrest, inhibited migration and excessive invasion in glioma cells. Pretreatment with the pan-caspase-inhibitor Z-VAD-FMK attenuated the PTE-induced apoptosis of glioma cells. Moreover, PTE significantly increased the production of reactive oxygen species (ROS) and reduce the mitochondrial membrane potential (MMP). Inhibition of ROS with N-acetyl-l-cysteine not only rescued PTE-induced reduction of cellular viability but also prevented glioma cell apoptosis. We also discovered ERK 1/2 and JNK signaling pathways were activated by PTE and contributed to induce glioma cell apoptosis. In addition, specific inhibitors of ERK 1/2 and JNK attenuated PTE-induced apoptosis. Besides, PTE significantly reduced tumor volume and prolonged median survival of tumor-bearing rats in vivo. In summary, the results of this study indicate that the anti-tumor effect of PTE on glioma cells may provide a new treatment option for glioma patients. |
format |
article |
author |
Haijun Gao Ziqiang Liu Weidong Xu Qunhui Wang Chaochao Zhang Yaonan Ding Weiguang Nie Jiacheng Lai Yong Chen Haiyan Huang |
author_facet |
Haijun Gao Ziqiang Liu Weidong Xu Qunhui Wang Chaochao Zhang Yaonan Ding Weiguang Nie Jiacheng Lai Yong Chen Haiyan Huang |
author_sort |
Haijun Gao |
title |
Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells |
title_short |
Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells |
title_full |
Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells |
title_fullStr |
Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells |
title_full_unstemmed |
Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells |
title_sort |
pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/eaae9165681e4b31bc97d6246ae0504d |
work_keys_str_mv |
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