Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress.
Casticin is one of the main active components obtained from Fructus Viticis and has been reported to exert anti-carcinogenic activity on a variety of cancer cells but the precise mechanism underlying this activity remains unclear.Apoptotic activities of casticin (1.0 µmol/l) and TRAIL (25, 50 ng/ml)...
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| Format: | Article |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3594187?pdf=render |
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| author | Yuan Zhou Li Tian Lingzhi Long Meifang Quan Fei Liu Jianguo Cao |
| author_facet | Yuan Zhou Li Tian Lingzhi Long Meifang Quan Fei Liu Jianguo Cao |
| author_sort | Yuan Zhou |
| collection | DOAJ |
| description | Casticin is one of the main active components obtained from Fructus Viticis and has been reported to exert anti-carcinogenic activity on a variety of cancer cells but the precise mechanism underlying this activity remains unclear.Apoptotic activities of casticin (1.0 µmol/l) and TRAIL (25, 50 ng/ml) alone or in combination in the gastric cancer cell lines BGC-823, SGC-7901 and MGC-803 were detected by the use of a cell apoptosis ELISA detection kit, flow cytometry (FCM) with propidium iodide (PI) staining and activities of caspase-3, -8 and -9 by ELISA and cleavage of polyADP-ribose polymerase (PARP) protein using western blot analysis. Death receptors (DR) expression levels were evaluated using FCM analysis and western blotting. 2', 7'-dichlorofluorescein diacetate (DCFH-DA) was used as a probe to measure the increase in reactive oxygen species (ROS) levels in cells. Multiple interventions, such as siRNA transfection and pharmacological inhibitors were used to explore the mechanisms of these actions.Subtoxic concentrations of casticin significantly potentiated TRAIL-induced cytotoxicity and apoptosis in BGC-823, SGC-7901 and MGC-803 cells. Casticin dramatically upregulated DR5 receptor expression but had no effects on DR4 or decoy receptors. Deletion of DR5 by siRNA significantly reduced the apoptosis induced by the co-application of TRAIL and casticin. Gene silencing of the CCAAT/enhancer binding protein homologous protein (CHOP) and pretreatment with salubrinal, an endoplasmic reticulum (ER) stress inhibitor, attenuated casticin-induced DR5 receptor expression, and apoptosis and ROS production. Casticin downregulated the expression levels of the cell survival proteins cFLIP, Bcl-2, XIAP, and survivin. In addition, casticin also induced the expressions of DR5 protein in other gastric cancer cells (SGC-7901 and MGC-803).Casticin enhances TRAIL-induced apoptosis through the downregulation of cell survival proteins and the upregulation of DR5 receptors through actions on the ROS-ER stress-CHOP pathway. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T21:28:16Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-722c8429c01649d69d51066fb177cb012022-12-22T01:32:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5885510.1371/journal.pone.0058855Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress.Yuan ZhouLi TianLingzhi LongMeifang QuanFei LiuJianguo CaoCasticin is one of the main active components obtained from Fructus Viticis and has been reported to exert anti-carcinogenic activity on a variety of cancer cells but the precise mechanism underlying this activity remains unclear.Apoptotic activities of casticin (1.0 µmol/l) and TRAIL (25, 50 ng/ml) alone or in combination in the gastric cancer cell lines BGC-823, SGC-7901 and MGC-803 were detected by the use of a cell apoptosis ELISA detection kit, flow cytometry (FCM) with propidium iodide (PI) staining and activities of caspase-3, -8 and -9 by ELISA and cleavage of polyADP-ribose polymerase (PARP) protein using western blot analysis. Death receptors (DR) expression levels were evaluated using FCM analysis and western blotting. 2', 7'-dichlorofluorescein diacetate (DCFH-DA) was used as a probe to measure the increase in reactive oxygen species (ROS) levels in cells. Multiple interventions, such as siRNA transfection and pharmacological inhibitors were used to explore the mechanisms of these actions.Subtoxic concentrations of casticin significantly potentiated TRAIL-induced cytotoxicity and apoptosis in BGC-823, SGC-7901 and MGC-803 cells. Casticin dramatically upregulated DR5 receptor expression but had no effects on DR4 or decoy receptors. Deletion of DR5 by siRNA significantly reduced the apoptosis induced by the co-application of TRAIL and casticin. Gene silencing of the CCAAT/enhancer binding protein homologous protein (CHOP) and pretreatment with salubrinal, an endoplasmic reticulum (ER) stress inhibitor, attenuated casticin-induced DR5 receptor expression, and apoptosis and ROS production. Casticin downregulated the expression levels of the cell survival proteins cFLIP, Bcl-2, XIAP, and survivin. In addition, casticin also induced the expressions of DR5 protein in other gastric cancer cells (SGC-7901 and MGC-803).Casticin enhances TRAIL-induced apoptosis through the downregulation of cell survival proteins and the upregulation of DR5 receptors through actions on the ROS-ER stress-CHOP pathway.http://europepmc.org/articles/PMC3594187?pdf=render |
| spellingShingle | Yuan Zhou Li Tian Lingzhi Long Meifang Quan Fei Liu Jianguo Cao Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress. PLoS ONE |
| title | Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress. |
| title_full | Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress. |
| title_fullStr | Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress. |
| title_full_unstemmed | Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress. |
| title_short | Casticin potentiates TRAIL-induced apoptosis of gastric cancer cells through endoplasmic reticulum stress. |
| title_sort | casticin potentiates trail induced apoptosis of gastric cancer cells through endoplasmic reticulum stress |
| url | http://europepmc.org/articles/PMC3594187?pdf=render |
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