Abstract |
Multi drug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of many human cancers. 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), a chalcone, isolated from the buds of Cleistocalyx operculatus, has been shown to have antitumor effects on human carcinoma SMMC-7721 cells in vitro and in vivo. In this paper, we studied the reversal effect and the mechanism of DMC on human hepatocellular carcinoma drug-resistant cells BEL-7402/5-FU in vitro. Administration of DMC reversed the multi-drug resistance of human hepatocellular carcinoma BEL-7402/5-FU cells significantly. DMC enhanced the sensitivity of BEL-7402/5-FU cells to 5-fluorouracil (5-FU) and doxorubicin (DOX). Staining with Hoechst 33258 and flow cytometric analysis showed that DMC has apoptosis-inducing effect on BEL-7402/5-FU cells. It could also increase the concentration of 5-FU in the resistant multi- drug-resistant cells. We also observed that over-expression of the multi-drug resistance-associated protein ( MRP1) and of the glutathione S-transferase π (GST-π) contributed to MDR in BEL-7402/5-FU cells. The mRNA expressions of MRP1 and GST-π and the protein expression of MRP1 were decreased by DMC. These data demonstrated that DMC could effectively reverse MDR in BEL-7402/5-FU cells.
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Authors | Hai-ya Huang, Jiang-long Niu, Li-ming Zhao, Yan-hua Lu |
Journal | Phytomedicine : international journal of phytotherapy and phytopharmacology
(Phytomedicine)
Vol. 18
Issue 12
Pg. 1086-92
(Sep 15 2011)
ISSN: 1618-095X [Electronic] Germany |
PMID | 21596545
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier GmbH. All rights reserved. |
Chemical References |
- 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone
- Antimetabolites, Antineoplastic
- Chalcones
- Fluorouracil
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Topics |
- Antimetabolites, Antineoplastic
(analysis)
- Carcinoma, Hepatocellular
(drug therapy)
- Cell Line, Tumor
(drug effects)
- Chalcones
(pharmacology, therapeutic use)
- Chromatography, High Pressure Liquid
- Drug Evaluation, Preclinical
- Drug Resistance, Neoplasm
(drug effects)
- Flow Cytometry
- Fluorouracil
(analysis)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Liver Neoplasms
(drug therapy)
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