<P><B>Abstract</B></P><P>Here, we reported the synthesis of a novel topoisomerase II inhibitor, MHY336, which that has strong topoisomerase-mediated anticancer activity but fewer side effects than other topoisomerase II i...
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https://www.riss.kr/link?id=A107756622
2011
-
SCOPUS,SCIE
학술저널
98-107(10쪽)
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P><B>Abstract</B></P><P>Here, we reported the synthesis of a novel topoisomerase II inhibitor, MHY336, which that has strong topoisomerase-mediated anticancer activity but fewer side effects than other topoisomerase II i...
<P><B>Abstract</B></P><P>Here, we reported the synthesis of a novel topoisomerase II inhibitor, MHY336, which that has strong topoisomerase-mediated anticancer activity but fewer side effects than other topoisomerase II inhibitors. The catalytic activity of MHY336 on the topoisomerase II enzyme was the same as that of the etoposide. In a cell-free system, MHY336 exhibited a potent activity on scavenging of reactive oxygen species against 3-morpholinosydnonimine hydrochloride (SIN-1)-induced oxidative stress. An <I>in vitro</I> cell-based assay demonstrated that MHY336 significantly inhibited the proliferation of three prostate cancer cell lines, LNCaP, PC-3, and DU145 cells. Notably, the cytotoxicity of MHY336 was more potent in LNCaP cells (IC<SUB>50</SUB>=1.39μM) than in DU145 (IC<SUB>50</SUB>=2.94μM) and PC3 cells (IC<SUB>50</SUB>=3.72μM). Furthermore, MHY336 treatment induced similar levels of cytotoxicity compared to doxorubicin treatment (IC<SUB>50</SUB>=1.55μM) in LNCap cells. Also, MHY336 significantly down-regulated topoisomerase II alpha expression and up-regulated p53 expression in LNCaP cells (wild-type p53), whereas it up-regulated the topoisomerase II alpha protein in both DU145 and PC3 cells (p53 mutated or deleted). MHY336 induced G2/M or S phase arrest in LNCaP cells through a well-documented topoisomerase II-dependent mechanism. Further studies using Annexin V-FITC binding assay, DAPI staining, and Western blot analyses illustrated that MHY336 markedly induced apoptotic cell death via the mitochondria-mediated intrinsic pathway in LNCaP cells. These results suggest that MHY336 is an attractive chemotherapeutic agent because of its topoisomerase II-mediated anti-tumour activity in human prostate cancer.</P>