Effects of Ganoderic acid Me on inhibiting multidrug resistance and inducing apoptosis in multidrug resistant colon cancer cells

Ganoderma lucidum is known as a valuable herb in the search for anticancer lead compounds because it has been used for thousands of years as a traditional medication. Triterpenoids are the principal active components in this fungus. Ganoderic acid Me (GA-Me), a pure lanostane triterpene, was isolate...

Full description

Saved in:
Bibliographic Details
Published in:Process biochemistry (1991) 2011-06, Vol.46 (6), p.1307-1314
Main Authors: Jiang, Zijing, Jin, Tiantian, Gao, Feng, Liu, Jianwen, Zhong, Jianjiang, Zhao, Heng
Format: Article
Language:English
Subjects:
antineoplastic agents
Apoptosis
caspase-3
caspase-9
colorectal neoplasms
cytosol
drug therapy
fungi
ganoderic acid
Ganoderic acid Me
Ganoderma lucidum
MDR1
membrane potential
messenger RNA
mitochondrial membrane
MRPs
Multidrug resistance
multiple drug resistance
neoplasm cells
protein synthesis
transcription (genetics)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Ganoderma lucidum is known as a valuable herb in the search for anticancer lead compounds because it has been used for thousands of years as a traditional medication. Triterpenoids are the principal active components in this fungus. Ganoderic acid Me (GA-Me), a pure lanostane triterpene, was isolated from G. lucidum. Our study showed that GA-Me could reverse the multidrug resistance (MDR) in multidrug resistant clone cancer cells. We investigated that GA-Me enhanced the chemosensitivities of anticancer agents in MDR cells. Furthermore, GA-Me inhibited the activity of hMDR1 promoter and this transcriptional suppression was consistent with the inhibitory effect of GA-Me on the mRNA and protein expression level of MDR1. Meanwhile, the expression levels of MRP1 and MRP2 were also inhibited by GA-Me. GA-Me could induce apoptosis in MDR cells via up-regulation of p-p53, p53, Bax, caspase-3, caspase-9 and down-regulation of Bcl-2. In addition, GA-Me stimulated the decline in mitochondrial membrane potential and cytochrome release into cytosol. We concluded that GA-Me could effectively reverse multidrug resistance in MDR colon cancer cells, via repressing expression levels of MDR1, MRPs and regulating apoptosis-related pathways. These results suggested that GA-Me had therapeutic potential against multidrug resistance as a new agent.
ISSN:1359-5113
1873-3298
DOI:10.1016/j.procbio.2011.02.023