Ganoderiol F inhibits topoisomerases and induces senescence of hepatoma cells, a strategy for cancer therapy
Date Issued
2005
Date
2005
Author(s)
Chang, Ue-Min
DOI
en-US
Abstract
Ganoderiol F (841), a tetracyclic triterpene isolated from Ganoderma amboinense, was found to be inhibitors of both topoisomerase I and topoisomerase IIα. Treatment of human hepatoma HepG2, Hep3B, Huh7 cells, and leukemia K562 cells with 841 resulted in immediate inhibition of DNA synthesis and halt of cell growth. On the other hand, the growth of normal lung fibroblast MRC5 cells were less affected and peripheral blood mononuclear cells were unaffected by 841. Furthermore, a senescent phenotype was detected in 841-treated HepG2 cells. Molecular events of senescence, including increase of p21 and p16, activation of p38 and p53 and the decrease of SIRT-1 as well as cyclin D1, were observed. Our study is the first report about 841 functioning as a senescence inducer in cancer cells and the tumor selective cytostatic effect and senescence induction capability of 841 might have anticancer implications. Low dosage of 841 (<1 μM) did not affect the viability of HepG2 cells but caused a significant decrease in the mRNA expression of hTERT, a reverse transcriptase subunit of telomerase, and detoxification in buthionine sulfoximine-treated cell, suggesting that low-dose of 841 may function as chemopreventive agent and inhibit tumorigenesis.
Subjects
靈芝醇
三帖類
拓樸異構酶
老化
癌症
Ganoderiol F
triterpene
topoisomerase
senescence
cancer
SDGs
Type
other
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