Objective The aim of the present study was to clarify the mechanism underlying glioma cell death upon oligomeric procyanidins (F2) exposure. Methods The cytotoxicity of F2 on U87 (human malignant glioblastoma cell lin...Objective The aim of the present study was to clarify the mechanism underlying glioma cell death upon oligomeric procyanidins (F2) exposure. Methods The cytotoxicity of F2 on U87 (human malignant glioblastoma cell line) and C6 (rat glioma cell line) cancer cells was evaluated, and changes of mitochondrial membrane potential (MMP) and production of reactive oxygen species (ROS) in drug-treated cells were monitored. Moreover, morphological changes associated with F2-induced cells death were examined. Results F2 induced a concentration-dependent increase in ROS production and decrease in MMP. Furthermore, pre-incubation with N-acetylcysteine (NAC) and rotenone (Rt), resulted in partial inhibition of F2-induced ROS generation and marked attenuation of cell death and the cytoplasmic vacuolization induced by F2. In addition, pretreatment with Rt markedly attenuated the MMP loss in F2-treated cells. However, pretreatment with NAC only markedly attenuated the MMP loss in F2-treated C6 cells. Conclusion The increase in ROS level is at least one of mechanisms associated with F2-induced glioma cell death as well as the cytoplasmic vacuolization formation that contribute to the cytotoxicity of F2 in glioma cells.展开更多
目的分析近20年来副凋亡研究现状、热点和发展趋势,为今后的研究提供参考。方法以副凋亡为主题在Web of Science数据库中检索并筛选于2003年1月1日至2023年12月31日发表的语言为英语的论著和综述,利用CiteSpace和VOSviewer软件生成知识...目的分析近20年来副凋亡研究现状、热点和发展趋势,为今后的研究提供参考。方法以副凋亡为主题在Web of Science数据库中检索并筛选于2003年1月1日至2023年12月31日发表的语言为英语的论著和综述,利用CiteSpace和VOSviewer软件生成知识图谱。结果共纳入305篇文献,副凋亡研究的发文量呈逐年递增趋势。中国(106篇)和亚洲大学(韩国)分别是发文量最多的国家和机构,美国与其他国家合作更频繁。刊文量较多的期刊为《Cell death disease》《Photochemistry and Photobiology》《Oncotarget》。关键词的热度分析显示线粒体功能障碍、内质网自噬、乳腺癌和肝细胞癌是该领域的研究热点。结论国内外副凋亡研究发展迅速,尤其在肿瘤学领域,信号通路将成为未来研究的重点。展开更多
The mammalian target of rapamycin(m TOR) pathway is abnormally activated in lung cancer.However, the anti-lung cancer effect of m TOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an a...The mammalian target of rapamycin(m TOR) pathway is abnormally activated in lung cancer.However, the anti-lung cancer effect of m TOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the m TOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2(labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. EveRh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased cMYC mediated the accumulation of tribbles homolog 3(TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.展开更多
Since inherent or acquired cellular resistance to various pro-apoptotic treatments often leads to therapeutic failure,a better understanding of alternative non-apoptotic pathways may facilitate the design of novel the...Since inherent or acquired cellular resistance to various pro-apoptotic treatments often leads to therapeutic failure,a better understanding of alternative non-apoptotic pathways may facilitate the design of novel therapeutics against malignant cancer cells.Paraptosis is a cell death mode characterized by extensive vacuolization that arises via dilation of the endoplasmic reticulum(ER)and mitochondria,without any apoptotic characteristics.We found that curcumin,dimethoxycurcumin(a more stable analog of curcumin),and celastol kill malignant cancer cells via induction of paraptosis as a main cell death mode.Study on the underlying mechanisms of paraptosis revealed that simultaneous proteasomal inhibition and mitochondrial Ca2+ overload can effectively induce paraptosis in cancer cells.Mitochondrial Ca2+ overload can be achieved not only by inhibition of mitochondrial Na+/Ca2+ exchanger but also by IP3 receptor-or ryanodine receptor-mediated release of Ca2+ from the ER and its subsequent mitochondrial Ca2+ uniporter-mediated Ca2+ influx into mitochondria.Since malignant cancer cells are more vulnerable to oxidative stress and ER stress than normal cells,clarification of the molecular basis of paraptosis that targets mitochondria and the ER at the same time may provide a rational therapeutic strategy for effectively killing resistant cancer cells.展开更多
基金supported by the Project of Key Laboratory for New Drug Screening of Liaoning Provinceby National Key Scientific Project for New Drug Discovery and Development,P. R.China (2009ZX09301-012)
文摘Objective The aim of the present study was to clarify the mechanism underlying glioma cell death upon oligomeric procyanidins (F2) exposure. Methods The cytotoxicity of F2 on U87 (human malignant glioblastoma cell line) and C6 (rat glioma cell line) cancer cells was evaluated, and changes of mitochondrial membrane potential (MMP) and production of reactive oxygen species (ROS) in drug-treated cells were monitored. Moreover, morphological changes associated with F2-induced cells death were examined. Results F2 induced a concentration-dependent increase in ROS production and decrease in MMP. Furthermore, pre-incubation with N-acetylcysteine (NAC) and rotenone (Rt), resulted in partial inhibition of F2-induced ROS generation and marked attenuation of cell death and the cytoplasmic vacuolization induced by F2. In addition, pretreatment with Rt markedly attenuated the MMP loss in F2-treated cells. However, pretreatment with NAC only markedly attenuated the MMP loss in F2-treated C6 cells. Conclusion The increase in ROS level is at least one of mechanisms associated with F2-induced glioma cell death as well as the cytoplasmic vacuolization formation that contribute to the cytotoxicity of F2 in glioma cells.
文摘目的分析近20年来副凋亡研究现状、热点和发展趋势,为今后的研究提供参考。方法以副凋亡为主题在Web of Science数据库中检索并筛选于2003年1月1日至2023年12月31日发表的语言为英语的论著和综述,利用CiteSpace和VOSviewer软件生成知识图谱。结果共纳入305篇文献,副凋亡研究的发文量呈逐年递增趋势。中国(106篇)和亚洲大学(韩国)分别是发文量最多的国家和机构,美国与其他国家合作更频繁。刊文量较多的期刊为《Cell death disease》《Photochemistry and Photobiology》《Oncotarget》。关键词的热度分析显示线粒体功能障碍、内质网自噬、乳腺癌和肝细胞癌是该领域的研究热点。结论国内外副凋亡研究发展迅速,尤其在肿瘤学领域,信号通路将成为未来研究的重点。
基金supported by the National Natural Science Foundation of China(No.81973516)partially supported by the Science and Technology Development Fund,Macao S.A.R,China(Nos.024/2016/A1 and 0129/2019/A3)University of Macao(No.CPG2021-00022-ICMS)。
文摘The mammalian target of rapamycin(m TOR) pathway is abnormally activated in lung cancer.However, the anti-lung cancer effect of m TOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the m TOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2(labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. EveRh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased cMYC mediated the accumulation of tribbles homolog 3(TRIB3)/P62+ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62+ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.
文摘Since inherent or acquired cellular resistance to various pro-apoptotic treatments often leads to therapeutic failure,a better understanding of alternative non-apoptotic pathways may facilitate the design of novel therapeutics against malignant cancer cells.Paraptosis is a cell death mode characterized by extensive vacuolization that arises via dilation of the endoplasmic reticulum(ER)and mitochondria,without any apoptotic characteristics.We found that curcumin,dimethoxycurcumin(a more stable analog of curcumin),and celastol kill malignant cancer cells via induction of paraptosis as a main cell death mode.Study on the underlying mechanisms of paraptosis revealed that simultaneous proteasomal inhibition and mitochondrial Ca2+ overload can effectively induce paraptosis in cancer cells.Mitochondrial Ca2+ overload can be achieved not only by inhibition of mitochondrial Na+/Ca2+ exchanger but also by IP3 receptor-or ryanodine receptor-mediated release of Ca2+ from the ER and its subsequent mitochondrial Ca2+ uniporter-mediated Ca2+ influx into mitochondria.Since malignant cancer cells are more vulnerable to oxidative stress and ER stress than normal cells,clarification of the molecular basis of paraptosis that targets mitochondria and the ER at the same time may provide a rational therapeutic strategy for effectively killing resistant cancer cells.
基金supported by the National Natural Science Foundation of China (No.81460561and No.81360502)Guangxi Natural Science Foundation (No. 2014GXNSFAA118225)the Program of Key Laboratory of High-Incidence-Tumor Prevention and Treatment(Guangxi Medical University),the Ministry of Education,China (No.GKE2018-09 and No.GK2018-11)
