Document Detail


Enhancement of cisplatin-induced apoptosis by β-elemene in resistant human ovarian cancer cells.
MedLine Citation:
PMID:  23277286     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
β-Elemene is a new anticancer compound extracted from the Chinese medicinal herb Rhizoma zedoariae. We have shown previously that β-elemene increases cisplatin cytotoxicity and enhances cisplatin sensitivity via blocking cell cycle progression at G2/M phase in resistant ovarian tumor cells. In the current study, we asked whether β-elemene-augmented cisplatin activity in ovarian carcinoma cells is mediated through the induction of apoptosis. Here, we show that β-elemene triggered apoptotic cell death in chemoresistant human ovarian cancer A2780/CP and MCAS cells in a dose- and time-dependent fashion, as assessed by six different apoptosis assays. Intriguingly, β-elemene was a stronger inducer of apoptosis than cisplatin in this model system, and a synergistic effect on induction of cell death was observed when the tumor cells were treated with both agents. Furthermore, β-elemene plus cisplatin exposure significantly disrupted the mitochondrial transmembrane potential (ΔΨ (m)) and increased the release of cytochrome c from mitochondria into the cytoplasm. The combination treatment with both compounds also induced increases in caspase-3/8/9 activities and caspase-9 cleavage, enhanced protein expression of Bax and phosphorylation of Bcl-2 at Ser-70, and reduced the protein levels of Bcl-2 and Bcl-X(L) in the platinum-resistant ovarian cancer cells. Taken together, these data indicate that β-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced apoptosis and that the augmented effect of β-elemene on cisplatin cytotoxicity and sensitivity in resistant ovarian tumor cells is mediated through a mitochondria- and caspase-dependent cell death pathway.
Authors:
Qingdi Quentin Li; Rebecca X Lee; Huasheng Liang; Yuhua Zhong; Eddie Reed
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-01
Journal Detail:
Title:  Medical oncology (Northwood, London, England)     Volume:  30     ISSN:  1559-131X     ISO Abbreviation:  Med. Oncol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-01     Completed Date:  2013-07-25     Revised Date:  2013-08-12    
Medline Journal Info:
Nlm Unique ID:  9435512     Medline TA:  Med Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  424     Citation Subset:  IM    
Affiliation:
Beihai Institute of Endocrine and Metabolic Diseases, Beihai, 536000 Guangxi, China. quentinli2004@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Blotting, Western
Cell Line, Tumor
Cisplatin / pharmacology
Drug Synergism
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Humans
In Situ Nick-End Labeling
Membrane Potential, Mitochondrial / drug effects
Ovarian Neoplasms*
Sesquiterpenes / pharmacology*
Grant Support
ID/Acronym/Agency:
P20RR16440-010003/RR/NCRR NIH HHS; P20RR16440-020003/RR/NCRR NIH HHS; P20RR16440-030003/RR/NCRR NIH HHS; P20RR16440-040003/RR/NCRR NIH HHS; T32 AR050958/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Sesquiterpenes; 0/beta-elemene; 15663-27-1/Cisplatin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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