Antileukemia component, dehydroeburicoic acid from Antrodia camphorata induces DNA damage and apoptosis in vitro and in vivo models

详细信息    查看全文

• 作者：Ying-Chi Du^a ; ¹ ; Fang-Rong Chang^a ; ^b ; ^c ; ^d ; ¹ ; Tung-Ying Wu^a ; Yu-Ming Hsu^a ; Mohamed El-Shazly^a ; ^e ; Chieh-Fu Chen^f ; Ping-Jyun Sung^g ; ^h ; Yan-Yu Lin^a ; Yi-Hsin Lin^a ; Yang-Chang Wu^a ; ⁱ ; ^j ; ^k ; ^{yachwu@mail.cmu.edu.tw} ; Mei-Chin Lu^a ; ^g ; ^h ; ^{jinx6609@yahoo.com.tw}
• 关键词：Antrodia camphorata ; Dehydroeburicoic acid (DeEA) ; DNA damage ; Apoptosis ; Topoisomerase II inhibitor
• 刊名：Phytomedicine
• 出版年：2012
• 出版时间：15 June, 2012
• 年：2012
• 卷：19
• 期：8-9
• 页码：788-796
• 全文大小：1395 K

文摘

Antrodia camphorata (AC) is a native Taiwanese mushroom which is used in Asian folk medicine as a chemopreventive agent. The triterpenoid-rich fraction (FEA) was obtained from the ethanolic extract of AC and characterized by high performance liquid chromatography (HPLC). FEA caused DNA damage in leukemia HL 60 cells which was characterized by phosphorylation of H2A.X and Chk2. It also exhibited apoptotic effect which was correlated to the enhancement of PARP cleavage and to the activation of caspase 3. Five major triterpenoids, antcin K (1), antcin C (2), zhankuic acid C (3), zhankuic acid A (4), and dehydroeburicoic acid (5) were isolated from FEA. The cytotoxicity of FEA major components (1-5) was investigated showing that dehydroeburicoic acid (DeEA) was the most potent cytotoxic component. DeEA activated DNA damage and apoptosis biomarkers similar to FEA and also inhibited topoisomerase II. In HL 60 cells xenograft animal model, DeEA treatment resulted in a marked decrease of tumor weight and size without any significant decrease in mice body weights. Taken together, our results provided the first evidence that pure AC component inhibited tumor growth in vivo model backing the traditional anticancer use of AC in Asian countries.