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Subamolide A, a component isolated from Cinnamomum subavenium, induces apoptosis mediated by mitochondria-dependent, p53 and ERK1/2 pathways in human urothelial carcinoma cell line NTUB1.
MedLine Citation:
PMID:  21708241     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIM OF THE STUDY: The goal of this work was to study the cytotoxic effect of subamolide A, a constituent isolated from the stems of Cinnamomum subavenium Miq., and to extend its traditional use for clinical applications in treating human urothelial carcinoma. MATERIALS AND METHODS: Cytotoxic effect of subamolide A was determined by the MTT assay in NTUB1, T24, PC3 and SV-HUC-1 cells treated with various concentrations of subamolide A for three days. Apoptosis was detected by the change of cell morphology and flow cytometry analysis. The reactive oxygen species (ROS) level and mitochondria membrane potential (Δψm) were determined by flow cytometry. Western blot analysis was used to quantify the expression of apoptosis-related and stress-induced signaling molecules. RESULTS: Subamolide A selectively induced apoptosis in two cancerous human urothelial carcinoma cell lines (NTUB1 and T24) in comparison with normal immortalized uroepithelial cells (SV-HUC-1). Subamolide A reduced mitochondrial membrane potential (Δψm) and caused apoptosis of NTUB1 cells. Subamolide A increased Bax/Bcl-2 ratios, the amount of cytochrome c released from the mitochondria, caspase-3 and PARP cleavage, activated p53 and ERK1/2 and ultimately led to apoptosis in NTUB1 cells. Furthermore, a higher dose (10μM) of subamolide A synergistically enhanced the cytotoxicity of cisplatin and gemcitabine in NTUB1 cells. CONCLUSIONS: The current study demonstrated that subamolide A triggered the mitochondria-dependent apoptotic pathways and p53 and ERK1/2 activation in the human urothelial carcinoma cell line NTUB1. In addition, subamolide A synergistically enhanced cytotoxic effect of CDDP and Gem in NTUB1. These data suggested that subamolide A exhibited a potent anti-proliferation activity. This study supports the traditional use of Cinnamomum subavenium stems with a therapeutic potential for the treatment of human urothelial carcinoma.
Authors:
Chiung-Hui Liu; Chung-Yi Chen; A-Mei Huang; Jih-Heng Li
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-17
Journal Detail:
Title:  Journal of ethnopharmacology     Volume:  -     ISSN:  1872-7573     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7903310     Medline TA:  J Ethnopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
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