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The herbal compound cryptotanshinone restores sensitivity in cancer cells that are resistant to the tumor necrosis factor-related apoptosis-inducing ligand
Tse A.K.-W.; Chow K.-Y.; Cao H.-H.; Cheng C.-Y.; Kwan H.-Y.; Yu H.; Zhu G.-Y.; Wu Y.-C.; Fong W.-F.; Yu Z.-L.
2013-10-11
Source PublicationJournal of Biological Chemistry
ISSN00219258 1083351X
Volume288Issue:41Pages:29923-29933
Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis and kills cancer cells but not normal cells. However, TRAIL resistance due to low level of TRAIL receptor expression is widely found in cancer cells and hampers its development for cancer treatment. Thus, the agents that can sensitize the tumor cells to TRAIL-mediated apoptosis are urgently needed. We investigated whether tanshinones, the major bioactive compounds of Salvia miltiorrhiza (danshen), can up-regulate TRAIL receptor expression. Among the major tanshinones being tested, cryptotanshinone (CT) showed the best ability to induce TRAIL receptor 2 (DR5) expression. We further showed that CT was capable of promoting TRAIL-induced cell death and apoptosis in A375 melanoma cells. CT-induced DR5 induction was not cell type-specific, as DR5 induction was observed in other cancer cell types. DR5 knockdown abolished the enhancing effect of CT on TRAIL responses. Mechanistically, induction of the DR5 by CT was found to be p53- independent but dependent on the induction of CCAAT/enhancer- binding protein-homologous protein (CHOP). Knockdown of CHOP abolished CT-induced DR5 expression and the associated potentiation of TRAIL-mediated cell death. In addition, CT-induced ROS production preceded up-regulation ofCHOPand DR5 and consequent sensitization of cells to TRAIL. Interestingly, CT also converted TRAIL-resistant lung A549 cancer cells into TRAIL-sensitive cells. Taken together, our results indicate thatCT can potentiate TRAIL-induced apoptosis through up-regulation of DR5. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI10.1074/jbc.M113.483909
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000330615300065
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Cited Times [WOS]:29   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
AffiliationHong Kong Baptist University
Recommended Citation
GB/T 7714
Tse A.K.-W.,Chow K.-Y.,Cao H.-H.,et al. The herbal compound cryptotanshinone restores sensitivity in cancer cells that are resistant to the tumor necrosis factor-related apoptosis-inducing ligand[J]. Journal of Biological Chemistry,2013,288(41):29923-29933.
APA Tse A.K.-W..,Chow K.-Y..,Cao H.-H..,Cheng C.-Y..,Kwan H.-Y..,...&Yu Z.-L..(2013).The herbal compound cryptotanshinone restores sensitivity in cancer cells that are resistant to the tumor necrosis factor-related apoptosis-inducing ligand.Journal of Biological Chemistry,288(41),29923-29933.
MLA Tse A.K.-W.,et al."The herbal compound cryptotanshinone restores sensitivity in cancer cells that are resistant to the tumor necrosis factor-related apoptosis-inducing ligand".Journal of Biological Chemistry 288.41(2013):29923-29933.
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