Effects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death
Gang Wang1,2, Jun Jie Wang1, Guang Yi Yang1, Shi Ming Du1, Nan Zeng2, Dong Sheng Li3, Rui Ming Li3, Ji Yan Chen1, Jin Bo Feng3, Shen Hao Yuan1, Fang Ye11Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, 2Department of Pharmacy, Chendu Traditional Chin...
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Dove Medical Press
2012
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oai:doaj.org-article:f47ba017412f45abb336ef6766b807d42021-12-02T02:49:27ZEffects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death1176-91141178-2013https://doaj.org/article/f47ba017412f45abb336ef6766b807d42012-01-01T00:00:00Zhttp://www.dovepress.com/effects-of-quercetin-nanoliposomes-on-c6-glioma-cells-through-inductio-a9066https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Gang Wang1,2, Jun Jie Wang1, Guang Yi Yang1, Shi Ming Du1, Nan Zeng2, Dong Sheng Li3, Rui Ming Li3, Ji Yan Chen1, Jin Bo Feng3, Shen Hao Yuan1, Fang Ye11Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, 2Department of Pharmacy, Chendu Traditional Chinese Medical University, Chendu City, Sichuan Province, 3Hubei Provincial Key Laboratory of Embryo Stem Cells, Shiyan City, Hubei Province, People's Republic of ChinaBackground: Quercetin has been shown to induce apoptosis in a number of cancer cell lines, but a quercetin-loaded nanoliposomal formulation with enhanced antitumor activity in C6 glioma cells and its effect on cancer cell death has not been well studied. The aim of this study was to examine if quercetin-loaded liposomes (QUE-NL) has enhanced cytotoxic effects and if such effects involve type III programmed cell death in C6 glioma cells.Methods: C6 glioma cells were treated with QUE-NL and assayed for cell survival, apoptosis, and necrosis. Levels of reactive oxygen species production and loss of mitochondrial membrane potential (ΔΨm) were also determined by flow cytometry assay to assess the effects of QUE-NL. ATP levels and lactate dehydrogenase activity were measured, and Western blotting was used to assay cytochrome C release and caspase expression.Results: QUE-NL induced type III (necrotic) programmed cell death in C6 glioma cells in a dose-dependent and time-dependent manner. High concentrations of QUE-NL induced cell necrosis, which is distinct from apoptosis and autophagy, whereas liposomes administered alone induced neither significant apoptosis nor necrosis in C6 glioma cells. QUE-NL-induced ΔΨm loss and cytochrome C release had no effect on caspase activation, but decreased ATP levels and increased lactate dehydrogenase activity indicated that QUE-NL stimulated necrotic cell death.Conclusion: C6 glioma cells treated with QUE-NL showed a cellular pattern associated with necrosis without apoptosis and was independent of caspase activity. Nonapoptotic cell death induced by high concentrations of QUE-NL for controlling caspase-independent type III programmed cell death may provide the basis for novel therapeutic approaches to overcome avoidance of apoptosis by malignant cells.Keywords: quercetin, liposome, type III programmed cell death, reactive oxygen species, ATP, mitochondria, C6 glioma cellsChen JY, Feng JBLi RMLi DSZeng NDu SMYang GYWang JJWang GYuan SHYe FDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 271-280 (2012) |
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Medicine (General) R5-920 Chen JY, Feng JB Li RM Li DS Zeng N Du SM Yang GY Wang JJ Wang G Yuan SH Ye F Effects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death |
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Gang Wang1,2, Jun Jie Wang1, Guang Yi Yang1, Shi Ming Du1, Nan Zeng2, Dong Sheng Li3, Rui Ming Li3, Ji Yan Chen1, Jin Bo Feng3, Shen Hao Yuan1, Fang Ye11Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, 2Department of Pharmacy, Chendu Traditional Chinese Medical University, Chendu City, Sichuan Province, 3Hubei Provincial Key Laboratory of Embryo Stem Cells, Shiyan City, Hubei Province, People's Republic of ChinaBackground: Quercetin has been shown to induce apoptosis in a number of cancer cell lines, but a quercetin-loaded nanoliposomal formulation with enhanced antitumor activity in C6 glioma cells and its effect on cancer cell death has not been well studied. The aim of this study was to examine if quercetin-loaded liposomes (QUE-NL) has enhanced cytotoxic effects and if such effects involve type III programmed cell death in C6 glioma cells.Methods: C6 glioma cells were treated with QUE-NL and assayed for cell survival, apoptosis, and necrosis. Levels of reactive oxygen species production and loss of mitochondrial membrane potential (ΔΨm) were also determined by flow cytometry assay to assess the effects of QUE-NL. ATP levels and lactate dehydrogenase activity were measured, and Western blotting was used to assay cytochrome C release and caspase expression.Results: QUE-NL induced type III (necrotic) programmed cell death in C6 glioma cells in a dose-dependent and time-dependent manner. High concentrations of QUE-NL induced cell necrosis, which is distinct from apoptosis and autophagy, whereas liposomes administered alone induced neither significant apoptosis nor necrosis in C6 glioma cells. QUE-NL-induced ΔΨm loss and cytochrome C release had no effect on caspase activation, but decreased ATP levels and increased lactate dehydrogenase activity indicated that QUE-NL stimulated necrotic cell death.Conclusion: C6 glioma cells treated with QUE-NL showed a cellular pattern associated with necrosis without apoptosis and was independent of caspase activity. Nonapoptotic cell death induced by high concentrations of QUE-NL for controlling caspase-independent type III programmed cell death may provide the basis for novel therapeutic approaches to overcome avoidance of apoptosis by malignant cells.Keywords: quercetin, liposome, type III programmed cell death, reactive oxygen species, ATP, mitochondria, C6 glioma cells |
format |
article |
author |
Chen JY, Feng JB Li RM Li DS Zeng N Du SM Yang GY Wang JJ Wang G Yuan SH Ye F |
author_facet |
Chen JY, Feng JB Li RM Li DS Zeng N Du SM Yang GY Wang JJ Wang G Yuan SH Ye F |
author_sort |
Chen JY, Feng JB |
title |
Effects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death |
title_short |
Effects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death |
title_full |
Effects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death |
title_fullStr |
Effects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death |
title_full_unstemmed |
Effects of quercetin nanoliposomes on C6 glioma cells through induction of type III programmed cell death |
title_sort |
effects of quercetin nanoliposomes on c6 glioma cells through induction of type iii programmed cell death |
publisher |
Dove Medical Press |
publishDate |
2012 |
url |
https://doaj.org/article/f47ba017412f45abb336ef6766b807d4 |
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