Document Detail


Enhancement of anticancer efficacy of chemotherapeutics by gambogic acid against gastric cancer cells.
MedLine Citation:
PMID:  22444164     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gambogic acid (GA), the main active component of gamboge, is well known for its marked antitumor effect in vitro and in vivo. The aim of this study was to assess the natural interaction between GA and chemotherapeutic agents, 5-fluorouracil (5-FU), oxaliplatin (Oxa), and docetaxel (Doc), which are widely used in gastric cancer treatment. This study also investigated the effect of GA on cell apoptosis and drug-associated gene expression for further mechanism research. Synergistic interaction on human gastric cancer BGC-823 cells and MKN-28 cells was evaluated using the combination index (CI) method. The double staining method with Annexin-V-FITC and PI was employed to distinguish the apoptotic cells from others. Expression of drug-associated genes, that is, thymidylate synthase (TS), excision repair cross-complementing (ERCC1), BRCA1, tau, and β-tubulin III, was measured by real-time quantitative RT-PCR. This study found that GA had a synergistic effect on the cytotoxity of chemotherapeutic agents against both cell lines. The combination of GA and chemotherapeutic agents could also induce apoptosis in a synergistic manner. The mRNA levels of TS, ERCC1, BRCA1, tau, and β-tubulin III were suppressed at 0.009, 0.075, 0.140, 0.267, and 0.624-fold, respectively, when cells were exposed to GA at the concentration of 0.25 μM. These data suggest that GA has a promising role in enhancing the efficacy of 5-FU, Oxa, and Doc in the treatment of gastric cancer. The potential mechanism would be their synergistic effects on apoptosis induction and the downregulation of chemotherapeutic agent-associated genes.
Authors:
Zheng-Yun Zou; Jia Wei; Xiao-Lin Li; Li-Xia Yu; Ting-Ting Wang; Xiao-Ping Qian; Bao-Rui Liu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-23
Journal Detail:
Title:  Cancer biotherapy & radiopharmaceuticals     Volume:  27     ISSN:  1557-8852     ISO Abbreviation:  Cancer Biother. Radiopharm.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-18     Completed Date:  2012-11-09     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  9605408     Medline TA:  Cancer Biother Radiopharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  299-306     Citation Subset:  IM    
Affiliation:
Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects
Cell Line, Tumor
Drug Synergism
Fluorouracil / administration & dosage,  pharmacology
Gene Expression
Humans
Organoplatinum Compounds / administration & dosage,  pharmacology
Stomach Neoplasms / drug therapy*,  genetics
Taxoids / administration & dosage,  pharmacology
Xanthones / administration & dosage,  pharmacology*
Chemical
Reg. No./Substance:
0/Organoplatinum Compounds; 0/Taxoids; 0/Xanthones; 15H5577CQD/docetaxel; 2752-65-0/gambogic acid; 51-21-8/Fluorouracil; 63121-00-6/oxaliplatin

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


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