Document Detail

A novel resveratrol derivative, HS1793, overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells.
MedLine Citation:
PMID:  19426672     Owner:  NLM     Status:  MEDLINE    
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 than resveratrol in most cancer cells tested. We further examined whether HS-1793, showing potent 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. We also observed that HS-1793 exerts its antitumor activity via Bad. However, overall data obtained from methylation specific PCR, RT-PCR and real-time PCR suggest that HS-1793 plays a role in the downregulation 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.
Seung Hun Jeong; Wol Soon Jo; Suhee Song; Hongsuk Suh; So-Young Seol; Sun-Hee Leem; Taeg Kyu Kwon; Young Hyun Yoo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-20
Journal Detail:
Title:  Biochemical pharmacology     Volume:  77     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-11     Completed Date:  2009-06-02     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1337-47     Citation Subset:  IM    
Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Medical Science Research Center, 3-1 Dongdaesin-dong, Seo-gu, Busan 602-714, South Korea.
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MeSH Terms
Antineoplastic Agents / chemical synthesis,  chemistry,  pharmacology*
Apoptosis / drug effects
Cell Nucleus / drug effects,  pathology
Cell Survival / drug effects
Drug Resistance, Neoplasm / drug effects*
Flow Cytometry
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects,  physiology
Molecular Structure
Naphthols / chemical synthesis,  chemistry,  pharmacology*
Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
Resorcinols / chemical synthesis,  chemistry,  pharmacology*
Reverse Transcriptase Polymerase Chain Reaction
Stilbenes / chemistry,  pharmacology*
U937 Cells
Reg. No./Substance:
0/4-(6-hydroxy-2-naphthyl)-1,3-benzenediol; 0/Antineoplastic Agents; 0/Naphthols; 0/Proto-Oncogene Proteins c-bcl-2; 0/Resorcinols; 0/Stilbenes; Q369O8926L/resveratrol

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