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A novel resveratrol derivative, HS1793, overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells

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Author(s)
Seung Hun JeongWol Soon JoSuhee SongHongsuk SuhSo-Young SeolSun-Hee LeemTaeg Kyu KwonYoung Hyun Yoo
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Institute for Medical Science (의과학연구소)
Journal Title
Biochemical Pharmacology
Issued Date
2009
Volume
77
Issue
8
Abstract
The chemopreventive and chemotherapeutic properties associated with resveratrol offer promise for the
design of new chemotherapeutic agents. However, resveratrol is not a potent cytotoxic compound when
compared with other chemotherapeutic drugs. Thus, several studies were undertaken to obtain synthetic
analogues of resveratrol with potent activity. The present study was undertaken to examine whether four
resveratrol analogues (HS-1784, -1792, -1791 and -1793) that we had designed and synthesized show
antitumor activity. Here, we observed that all of these resveratrol analogues displayed stronger antitumor
effects thanresveratrol inmostcancer cells tested.We further examinedwhetherHS-1793, showingpotent
antitumor effects in most cancer cells tested, overcomes the resistance conferred by Bcl-2, since
overcoming the resistance conferred by Bcl-2 represents an attractive therapeutic strategy against cancer.
Our viability assay showed that HS-1793 overcomes the resistance conferred by Bcl-2 in human leukemic
U937 cells. Various apoptosis assessment assays demonstrated that HS-1793 overcomes the resistance
conferred by Bcl-2 in human leukemic U937 cells by inducing apoptosis. Noticeably, we elucidated the
marked downregulation of 14-3-3 protein by HS-1793, indicating that HS-1793 overcomes the resistance
conferred by Bcl-2 in U937 cells via 14-3-3.Wealso observed that HS-1793 exerts its antitumor activity via
Bad.However, overall data obtained frommethylation specific PCR, RT-PCR and real-timePCR suggest that
HS-1793 plays a role in thedownregulation of 14-3-3 at a post-transcriptional level. Further understanding
exactly how HS-1793 overcomes the resistance conferred by Bcl-2 via 14-3-3 may guide the development
of future anticancer agents.
Crown Copyright 2009 Published by Elsevier Inc. All rights reserved
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Seung Hun Jeong et al. (2009). A novel resveratrol derivative, HS1793, overcomes the resistance conferred by
Bcl-2 in human leukemic U937 cells. Biochemical Pharmacology, 77(8), 1337–1347. doi: 10.1016/j.bcp.2009.01.002
Type
Article
ISSN
0006-2952
Source
https://www.sciencedirect.com/science/article/pii/S0006295209000057?via%3Dihub
DOI
10.1016/j.bcp.2009.01.002
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33699
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
3. Research Institutues (연구소) > Institute for Medical Science (의과학연구소)
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