Document Detail


Tubeimoside-1 exerts cytotoxicity in HeLa cells through mitochondrial dysfunction and endoplasmic reticulum stress pathways.
MedLine Citation:
PMID:  19215086     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Traditional Chinese herbal medicines are a great source of cancer chemotherapeutic agents. Tubeimoside-1 (TBMS1) is a triterpenoid saponin extracted from Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae), a Chinese herb with anticancer potential named as "Tu Bei Mu". In the present study, we used proteomics to examine the cytotoxic effects of TBMS1 on HeLa cells. Protein profiling of TBMS1-treated HeLa cells revealed profound protein alterations related to energy metabolism and protein synthesis and folding, suggesting that mitochondria and endoplasmic reticulum (ER) play a role in TBMS1-initiated apoptosis. TBMS1 induced the depletion of mitochondrial transmembrane potential (DeltaPsi(m)), leading to the activation of caspase-dependent apoptotic cell death. Unfolded Protein Response (UPR) signaling pathways are also activated after TBMS1 treatment and these changes were accompanied by increased expression of GADD153/CHOP, a transcription factor associated with growth arrest and apoptosis in the event of prolonged ER stress. Salubrinal (Sal), a selective inhibitor for ER stress, partially abrogated the TBMS1-related cell death. These results suggest that TBMS1 exerts cytotoxicity in HeLa cells through both mitochondrial dysfunction and ER stress cell death pathways.
Authors:
Yang Xu; Jen-Fu Chiu; Qing-Yu He; Feng Chen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of proteome research     Volume:  8     ISSN:  1535-3893     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-06-08     Completed Date:  2009-07-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1585-93     Citation Subset:  IM    
Affiliation:
School of Biological Sciences, and Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects,  physiology
Cell Line, Tumor
Cell Survival / drug effects
Drugs, Chinese Herbal / pharmacology*
Electrophoresis, Gel, Two-Dimensional
Endoplasmic Reticulum / drug effects,  physiology*
Hela Cells
Humans
Mitochondria / drug effects,  physiology*
Saponins / pharmacology*
Signal Transduction
Transcription Factor CHOP / metabolism
Triterpenes / pharmacology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/DDIT3 protein, human; 0/Drugs, Chinese Herbal; 0/Saponins; 0/Triterpenes; 102040-03-9/tubeimoside I; 147336-12-7/Transcription Factor CHOP

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